Before I discuss the main topic of weight loss maintenance, it would help to give you a brief overview of obesity. The world is in the grip of an obesity epidemic. In my post ‘What is obesity – is it merely about BMI?‘ I had defined obesity as “excessive body fat accumulation (not weighing too much), which is associated with clear risks to health.” In my post, Is obesity a disease or risk factor for other conditions? I had discussed the magnitude of obesity and had also highlighted that today most of the major international and national health organisations, including the World Health Organization (WHO), World Obesity Federation, and American Medical Association recognise obesity as a disease. In my post Complications of Obesity: the mother of all diseases I had discussed how obesity affects almost every aspect of health, from reproductive and respiratory function to memory and mood; it decreases both the lifespan and the quality of life and increases costs of health care, both at the individual as well as at the national level.
However, rather than considering obesity in a conventional way, one aspect that needs serious consideration is that normal weight doesn’t always equal ‘healthy weight’. In my post ‘Normal Weight Obesity – a myth or a reality? I had described individuals who have weight within normal limits according to the BMI but have a high body fat percentage and are predisposed to the same health risks as in ‘obesity’. Another worrying trend is the increasing incidence of Childhood obesity.
Lifestyle modifications encompassing dieting, physical activity and behavioural modifications often lead to weight loss. However, over the long term, the vast majority of individuals regain the weight they have lost. The trajectory of weight change during/after behavioural weight management interventions mostly follow a typical pattern; the obesity interventions typically result in early rapid weight loss followed by a weight plateau and then progressive regain. Thus, the main challenge of obesity treatment is not weight loss, but long-term weight loss maintenance.
The interaction between biology, environment and behaviour is central to weight loss efforts and the problem of weight regain. The collective input from the interaction between these pressures ultimately determines a “steady-state weight” in an individual. A significant change in any of these inputs has the potential to disturb the existing balance, induce a weight change, and evoke responses affecting a new “steady-state” weight. Accordingly, when the environment is altered by dieting and/or physical activity, in response to the resultant decreased energy stores (weight loss) and negative energy balance, there is a coordinated decrease in energy expenditure (biology) and increase in responsivity to food-related cues (behaviour).
The potency of these biological (metabolic) and behavioural responses determines the degree of weight loss, the duration of sustained weight loss at a lower steady-state, and the ability of the individual to sustain the diet and other weight loss efforts. These adaptations are designed to not only prevent continual weight loss, but they also create the biological pressure to return the body to its original weight. Thus, this relapse has a strong physiological basis and is not simply the result of the voluntary resumptions of old habits. To develop more effective weight loss maintenance strategies, an understanding of the mechanistic interactions between these pressures resulting in response to weight loss needs to be enhanced.
Defining success in weight loss maintenance
The proportion of individuals who successfully maintain weight loss varies according to how ‘successful maintenance of weight loss’ is defined. The definition must include the criterion for the magnitude of weight loss and duration of maintenance. Over recent years, goal setting for ‘successful’ obesity treatment has changed markedly; various studies have convincingly proven that modest but sustained weight loss is of considerable benefit to obese patients. As discussed under ‘setting weight-loss targets’ in my post ‘Diet Plan for Weight Loss – It’s going to be a journey’, expert panels and governmental guidelines now recommend that obese persons must aim to achieve modest (i.e. reasonable) reductions in body weight rather than striving for ideal weight. Currently, World Health Organization, the Institute of Medicine of the National Academy of Sciences, USA, and the National Heart Lung and Blood Institute of USA recommend that an overweight/obese persons should initially set a target of losing 5 to 15% of the current body weight, depending on the degree of obesity. As highlighted in the preceding sections these modest reductions in body weight can lead to substantial improvements in the risk of various disease conditions associated with obesity and improve psychological functioning, in particular, mood, body image and binge eating. Thus, if the focus is on overall health, achieving and maintaining weight losses of 5% to 15% of initial body weight should be considered successful, even though for many obese individuals this weight loss may not return them to a non-obese state.
Based on the criteria of health benefits of weight loss, in the last more than two decades, several definitions have been proposed to define “successful weight loss maintenance”. One of the most commonly used definitions was Proposed by Wing and Hill in their article titled ‘Successful Weight Loss Maintenance’ published in the journal Annual Review of Nutrition in July 2001. They proposed that successful weight loss maintainers should be defined as “individuals who have intentionally lost at least 10% of their body weight and kept it off at least one year”.
Several aspects of this definition need to be noted. Firstly, the definition requires that weight loss be intentional. Several recent studies suggest that unintentional weight loss occurs frequently in the population. Because the causes and consequences of unintentional weight loss are likely to differ from those associated with intentional weight loss, it is important to distinguish between the two. Secondly, the 10% criterion was suggested, because as discussed, weight loss of this magnitude significantly reduces the risk of developing type 2 diabetes and heart disease in susceptible people, and eliminates most of the other risks associated with obesity. Finally, the 1-year duration criterion was proposed in keeping with the US Institute of Medicine (IOM) definition. Besides, the authors believed that selecting this criterion may stimulate research on the factors that enable individuals, who have maintained their weight loss for one year, to maintain it through longer intervals. However, it is obvious that the term “successful” would require a much longer period of weight loss maintenance, hopefully lifelong.
Another definition was proposed by Rossner in his article titled ‘Defining success in obesity management’ published in the journal International Journal of Obesity and Related Metabolic Disorders in Mar 1997. He proposed that a sustained weight loss of about 5% to 10% of baseline body weight represents a definite degree of success. This goal has also been recommended by the 2013 AHA/ACC/TOS Guideline for the management of overweight and obesity: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society published in the Journal ‘Circulation’ in Jun 2014.
The aforementioned definitions emphasise on the notion that successful weight loss maintenance does not necessarily imply a large amount of weight loss, but that a modest 5% to 10% of the baseline body weight is sufficient to produce the various health benefits discussed above.
Regulation of body weight
Before discussing the factors contributing to weight gain, physiological responses that resist weight loss, as well as behavioural correlates of successful weight loss maintenance, it would be pertinent to discuss the processes involved in the regulation of body weight.
Processes involved in the regulation of body weight
Bodyweight is centrally regulated with peripheral hormonal signals released from the gastrointestinal tract, pancreas, and adipose tissue integrated primarily in the hypothalamus to regulate food intake and energy expenditure. Under steady-state conditions, energy intake (food) is metabolised and used to fuel basal metabolism, thermogenesis and our energy expenditure (physical activity); any excess energy intake is stored as fat in adipose tissue for later use. Maintaining a constant energy balance between energy intake and output requires a very precise level of control; even a subtle but sustained mismatch between energy intake and energy expenditure can cause weight gain. For example, a positive balance of as few as 10 calories a day, over and above the daily energy needs, sustained for a year would result in an excess intake of 3650 kcal (365 X 10 = 3650) in one year; this could potentially result in a gain of one pound over a year. To sustain weight gain over years, a positive balance must be sustained that results in substantive increments in absolute intake; however, the balance only needs to be positive by a small amount on daily basis.
The steady-state body weight is influenced by several different factors; these factors fall into 4 distinct but interrelated categories: homeostatic, hedonic, environmental and behavioural processes.
The homeostatic processes (or physiological processes) are related to nutritional needs and monitor available energy within the blood and fat stores. The homeostatic system comprises hormonal regulators of hunger, satiety, and adiposity levels, which act on hypothalamic and brain stem circuits to stimulate or inhibit feeding to maintain appropriate levels of energy balance. The hypothalamus (a small region of the brain located directly above the brain stem; it is a key regulator of homeostasis and pituitary [the master gland] function) is the main brain centre containing a complex network of neuronal (relating to a neuron [nerve cells] or neurons) mechanisms in charge of regulating hunger, satiety and energy balance.
Hypothalamus receives and integrates information from the central nervous system via the vagus nerve (carries an extensive range of signals from digestive system and organs to the brain and vice versa) and peripheral systems such as digestive system, and adipose tissue via various hormones. While signals from the digestive system convey information regarding energy balance (nutrient availability), signals from the adipose tissue convey information regarding energy stores (adiposity). People who experience significant food deprivation and are in an acute state of caloric need are considered to be in a state of homeostatic or physiological hunger.
Food intake and energy metabolism are regulated by a complex interaction between orexigenic, which stimulate hunger, and anorexigenic, which suppress hunger and induce satiety, hormones and neuropeptides (small protein-like molecules, produced and released by neurons, which are considered key mediators in the communication between neurons and effector cells) in the hypothalamus and peripheral tissues. Orexigenic hormones and peptides include ghrelin (also called the hunger hormone), produced and released mainly by the stomach, with small amounts also released by the small intestine, pancreas and brain; Neuropeptide Y (NPY), Agouti-related peptide (AGRP), orexins A & B, and melanin-concentrating hormone (MCH), produced and released by the hypothalamus. Anorexigenic hormones and peptides include leptin from the adipose tissue, cholecystokinin (CCK), Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the gut and pancreatic polypeptide (PP), amylin and insulin from the pancreas.
In simple terms, the physiological system regulating body weight is a feedback loop (a biological process in which some of the output of a system returns as input to exert some control in the process; feedback is negative when the return exerts an inhibitory control; positive when it exerts a stimulatory effect) between the hypothalamus and periphery, whereby hypothalamus responds to peripheral signals regarding energy stores (adiposity or the total fat mass) and energy balance by adjusting autonomic, neuroendocrine, behavioural and metabolic systems to achieve energy homeostasis. During energy deficiency, the expression of hunger signals is raised, ghrelin in the stomach and neuropeptide Y and orexins in the hypothalamus. In response to food intake, various satiety signals, e.g. cholecystokinin, glucagon-like peptide 1, and peptide YY are released from the intestine to reach the circulation, signalling to neurons in the brain through vagal afferents (an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS). Insulin and leptin are also mobilised to induce satiety, adipose tissue releasing leptin in proportion to the weight of the fat mass.
The homeostasis regulation and maintenance of stable body weight depend on the integration of these signals and on the ability to respond appropriately through modulation of energy expenditure and food intake. Broadly, as discussed in the preceding sections, leptin conveys information about long-term energy balance (i.e. energy stores in the form of adipose tissue) and acts on the hypothalamus to reduce food intake and increase energy expenditure. Most other hormones regulate short-term food intake (that is nutrient availability).
This metabolic regulation of body weight centres around the ‘body weight set point’. A popular, well-known theory, the ‘set point theory’, states that “every individual, whether lean or obese, has a well-regulated internal control mechanism that strives to maintain a pre-set level of body weight and/or body fat within a limited range.” This metabolic body weight set point has a genetic basis. Change in body weight, above or below the set point body weight, as a result of energy imbalance, elicits a compensatory increase or decrease in energy intake and energy expenditure, in an opposite direction, in order to restore the original set-point body weight. As highlighted above, energy balance is regulated by the hypothalamus based on the hormonal feedbacks about energy stores and nutrient availability, received from the periphery. Any change in the body weight, and thus the energy stores, is communicated to the hypothalamus through an array of hormones which regulate appetite. Hypothalamus, in turn, activates opposite sets of metabolic reactions in order to restore the set-point body weight. For example, the hormone leptin, derived from adipose tissue, is produced in proportion to the adipocyte size and fat mass, and thus acts as an indicator of the body’s fatness (energy stores). Increased level of leptin in the circulation, associated with a gain in body weight, activates the hypothalamus, which in turn, increases energy expenditure by increasing the resting metabolic rate and reduces energy intake by suppressing appetite, so as to promote weight loss. In contrast, decreased levels of leptin, associated with weight loss, results in slowing down of resting metabolic rate to conserve energy and increases intake of food, so as to promote weight gain. As discussed above, in addition to leptin, hypothalamus and other specific regions of the brain, receive numerous other feedback signals that in various ways reflect the body’s energy status.
Limitations of set-point theory
Even though there is now overwhelming experimental evidence to support the homeostatic regulation of body weight, a major drawback of this concept of a set-point is that it fails to explain the current obesity epidemic. The basic question that arises is that if bodyweight is determined by a genetically programmed set-point, then why are more and more people becoming obese now than just a few decades ago, even though population genome pool has not changed over this period. Secondly, if the body has a system by virtue of which the bodyweight will always return to an individual’s set point range, no matter how much it deviates from the set-point, then why should consuming unhealthy or junk food matter?
Recently evidence has emerged that even though the bodyweight set-point has a genetic basis, it is modifiable by environmental factors too, mainly the food intake. As stated above, set point theory suggests that body tends to maintain a pre-set level of body weight and/or body fat in a limited range and deviation of body weight from this set-point elicits compensatory changes in energy intake and expenditure in opposite direction, to restore the energy equilibrium and the original set-point body weight. However, there is evidence to suggest that if the positive energy balance is sufficiently large and sustained for long enough period, the persistent weight gain overcomes the physiological mechanisms which attempt to defend the set-point body weight, leading to an upward shift of the body weight set-point and body will now defend this new set-point. If the calorie intake is further increased and sustained for long periods, over time you develop a series of set-points that your body will attempt to defend.
A dynamic equilibrium model of body weight
This model is in accordance with the dynamic equilibrium model of body weight. An initial increase in energy intake, even if sustained over a long period, will not lead to a large, linear weight gain. Instead, as the energy intake increases and body weight starts to increase, compensatory changes set in to increase energy expenditure. The increase in energy expenditure is the result of changes in three processes – increased resting energy expenditure (REE), activity energy expenditure (AEE) and thermic effect of food (TEF). The REE is increased as a result of an increase in both fat and lean body mass; AEE is increased due to the increased cost of moving a heavier body weight and TEF is increased due to higher food intake and increased protein turn-over (due to gain of lean tissue) and its associated cost. As a result, the gap between energy intake and expenditure becomes lower and lower to reach a point of new equilibrium where without actually changing your energy expenditure yourself, your energy intake now matches your energy expenditure and this new equilibrium will now be defended. Obesity resulting from an elevation of the metabolic set point, which is characterised by an elevated body weight, which is metabolically defended just as normal body weight is defended at its set point, is termed ‘metabolic obesity.’
“There is no sincere love than the love of food.”– George Bernard Shaw
If eating behaviour were only regulated by homeostatic systems, food consumption would simply be in consonance purely with the biological needs of the body and the vast majority of people would maintain healthy body weight. However, the last few decades have seen a dramatic change in the food environment, leading to an unprecedented societal phenomenon wherein energy-dense and palatable foods are increasingly available and served in larger portions. In such an environment, eating behaviour is not only regulated by homeostatic mechanisms to meet the energy needs but in modern times an increasing proportion of human food consumption appears to be driven by pleasure.
The regulation of food intake is a complex system based on an intricate feedback system and in addition to metabolic systems, brain reward systems also play an important role in feeding behaviour. In general bland tasting foods are not eaten to excess, whereas palatable foods can stimulate feeding even when energy requirements have been met, contributing to weight gain and obesity. Research findings have demonstrated that palatable foods with high fat and sugar content activate the brain reward system to affect feeding behaviour; people experience subjective pleasure when eating palatable foods and enjoy the presentation of the meal, its aroma, texture and even the sound of chewing crunchy foods. All these stimuli activate the brain reward system, generating subjective pleasure sensations that can even lead an individual to eat compulsively.
Besides, hormonal regulators of appetite can influence food intake in part by modulating hedonic responses to food. Typical of “reward eating” is that the driving force is gratification rather than energy deficit. In evolutionary terms, this property of palatable foods used to be advantageous because it ensured that food was eaten when available, enabling energy to be stored in the body (as fat) for future need in environments where food sources were scarce and/or unreliable. However, in modern societies where food is widely available this adaptation has become a liability.
Until recently, most studies focused on the role of appetite regulation and homeostatic signals such as metabolic hormones and the availability of nutrients in the blood. However, it is becoming increasingly evident now that homeostatic and reward circuitry act in a concert to promote eating behaviours under conditions of deprivation and to inhibit food intake under conditions of satiety. In fact, the hedonic reward pathways can override the homeostatic regulatory system for energy balance, that would otherwise act to maintain stable body weight, thereby contributing to overeating energy-rich foods, despite physiologic satiation and replete energy stores. Thus, homeostatic control over food intake is usually secondary to hedonic (non-homeostatic) control, even for determining how much a person will eat in any given meal. It has been suggested that, rather than something being ‘wrong’ with homeostatic control of food intake, the system is insufficiently powered to cope with radical environmental changes and, thus, overwhelmed to the point where activation of the hedonic pathways becomes a major driving force for overconsumption. In other words, hedonic eating is governed by the reward system to satisfy the need for pleasure and is non-homeostatic with regard to energy balance. The term ‘hedonic hunger‘ refers to one’s preoccupation with and desire to consume foods for the purpose of pleasure and in the absence of physical hunger. In individuals susceptible to developing disorders of the hedonic system, there is a strong desire to consume energy-rich foods, despite a state of satiety and abundant energy stores, potentially stimulating weight gain. Thus, despite the inherent logic and appeal of the dietary strategies for weight loss and maintenance, the successful implementation of dietary modification is difficult because of the physiology associated with the hedonic reward system. Hedonic processes intricately interact with homeostatic hypothalamic processes, which operate completely outside our awareness; as a result, hedonic processes are also not entirely under conscious control. It is therefore unlikely that obese individuals can simply ‘will’ themselves to weight loss. Obesity resulting from sustained hedonic over-eating despite satiation and replete energy stores is termed as ‘hedonic obesity’.
Brain reward system
Rewards are defined as those objects, which we will work to acquire through the allocation of time, energy, or effort; that is any object or goal that we seek. For most people, a ‘reward’ is something desired because it produces a conscious experience of pleasure and thus the term may be used to refer to the psychological and neurobiological events that produce subjective pleasure. Rewards are crucial for individual and support elementary processes such as drinking, eating and reproduction.
The neural system that mediates the experience of reward consists of a network of brain regions that are activated whenever we experience something rewarding like using an addictive drug. When exposed to a rewarding stimulus the brain responds by increasing the release of the neurotransmitter dopamine. Thus, structures that are considered part of the reward system are found along the major dopamine pathways in the brain. The pathway most often associated with reward is the mesolimbic dopamine pathway, which starts in an area of the brain stem called Ventral Tegmental Area or VTA and is thought to play a primary role in the reward system. The VTA is one of the principal dopamine-producing areas in the brain and the mesolimbic dopamine pathway connects it with nucleus accumbens, a nucleus found in part of the brain that is strongly associated with motivation and reward, called the ventral striatum.
When we use an addictive drug or experience something rewarding such as food or romantic love, dopamine neurons in the VTA are activated. These neurons project to the nucleus accumbens via the mesolimbic dopamine pathway and their activation causes the dopamine levels in the nucleus accumbens to rise. Another major dopamine pathway, the mesocortical pathway also originates in VTA but travels to the cerebral cortex, specifically to the frontal lobes. It is also activated during rewarding experiences and is considered part of the reward system. Because of the overlap between these two systems they are often collectively referred to as the mesocorticolimbic system. The frontal lobes, in turn, provide descending projections to the nucleus accumbens and the ventral tegmental area. This mesocorticolimbic circuit then is a key player in the final common pathway that processes reward signals and regulates motivated behaviour.
While mesolimbic dopamine pathway, which is consistently activated during rewarding experiences, is considered to be the main structure of the reward system, which plays a key role in weight loss maintenance, the actual network of brain structures involved in mediating reward is much larger and more complex than just this dopamine pathway involving many other brain regions and neurotransmitters. Two other important neurotransmitters, apart from dopamine, involved in the reward system are opioid system (opioids are substances that have effects similar to those of morphine. Two important endogenous [produced within the body] opioids are beta-endorphin and encephalins) and serotonin.
Role of palatability in activation of brain reward system
Food is a primary stimulus essential for survival that can activate rewarding brain circuits through at least 3 senses: taste, smell and sight. Certain foods, particularly those rich in sugars and fat, are potent rewards that promote eating (even in the absence of an energetic requirement) and trigger learned associations between the stimulus and the reward (conditioning). Palatability or the hedonic value of food refers to the pleasure experienced when food is consumed. This sensation depends on the organoleptic properties i.e. its taste smell, colour or texture, and significantly influences the choice of food and its consumption.
Palatability apparently has a strong impact on satiation and possibly also exerts some influence on the regulation of satiety. Some studies have demonstrated that appetite increases with palatability, leading to increased food intake. As discussed, the hypothalamus has been recognised as the centre of homeostatic regulation; however, palatable foods can lead to impairments of normal appetite regulation. Besides disrupting appetite regulation, palatable foods induce pleasure and reward.
Food vs. drugs
Long-term overconsumption of palatable food has been compared to drug addiction with many common food substances being compared to drugs typically abused by humans, such as nicotine, alcohol, marijuana, methamphetamine, cocaine, and opioids. This is because palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. Drug abuse and palatable food with high fat and sugar content can significantly activate the dopamine reward circuitry; both have powerful reinforcing effects that are mediated, in part, by abrupt dopamine increases in the brain reward system. However, with repeated exposure to the food reward, the dopamine response habituates; excessive consumption of palatable energy-dense food can lead to a profound state of reward hyposensitivity (hypo ~ less than normal; responsivity ~ the degree to which something is responsive; responsiveness) of reward regions to food (i.e. reduced reward region response to palatable food intake) that is similar to that of drug abuse. This deficit in the reward circuitry leads them to repeatedly overeat to compensate for this deficiency.
The typical behaviour induced by stimulating the reward system is to “come back for more”. Accordingly, free access to palatable food may lead to overeating, characterised by prolongation of the meal, because the normally induced sensation of satiety is overridden.
Cognitive regulation of food craving
Cognitive regulation refers to the self-directed regulation of cognition (thoughts, beliefs, affects) toward the attainment of goals. Studies have demonstrated that in humans, behavioural drives for palatable food are moderated by cognition, specifically executive functions (the higher-level cognitive skills you use to control and coordinate your other cognitive abilities and behaviours), which support self-regulation of eating behaviour. There is increasing evidence that obesity is associated with impairment of certain cognitive functions, such as executive function, attention and memory. In fact, the ability to inhibit the urges to eat desirable food varies among individuals and might be one of the factors that contribute to their vulnerability for overeating.
The obesogenic environment in which we live, where highly palatable food is readily available, challenges our limited physiological resources to suppress food intake. A major dilemma we face almost on daily basis involves balancing between our internal goals (i.e. our beliefs/knowledge about healthy eating etc which guide our behaviour) with the consequences of eating highly palatable food that is ubiquitous. This interplay between cognition and reward is a fundamental component of the regulation of food intake in humans. Recent studies using functional magnetic resonance imaging (fMRI) have demonstrated the ability to suppress the rewarding effects of food.
Environmental influences on cognitive control of food reward
Interactions between the brain systems associated with cognition, reward and homeostasis do not occur in isolation; regulation of food intake, particularly the modulatory effect of cognitive control over food reward, occurs within the context of multiple levels of environmental influences. There are broadly 4 levels of influence in this model: Level-1 is at the individual-level; it refers to the biological, genetic, demographic, and learning history influences within any person. Level-2 is the family environment; the individual level is nested within the family environment and is influenced by elements such as role modelling, feeding styles, provision and availability of foods and other aspects of the home food environment. Level 3 is the ‘microenvironmental’ levels; it refers to the local environment or community in which the family and home are immediately nested. This includes local schools, playgrounds, walking areas, and shopping markets that enable or impede healthful eating behaviours. And finally, Level 4, the ‘macro-environmental’ level refers to the broader regional, state, national and international economic and industry policies and laws which can affect individual choices.
This model “recognises the importance of both the nesting of levels within one another and reciprocal influences among levels.” Each level offers a potential avenue for change, for helping individuals, families and communities achieve the diet and lifestyle recommendations.
Long-term weight management is extremely challenging due to interactions between our biology, behaviour and the obesogenic environment (an environment that promotes high energy intake and sedentary behaviour. This includes the foods that are available, affordable, accessible and promoted; physical activity opportunities; and the social norms in relation to food and physical activity). Contributing factors to this environment include intense marketing of energy-dense foods, increased availability of these foods and increased portion sizes, which all present people with the opportunity to over-consume large portions of sugary and high-fat foods. Moreover, a high level of stress associated with modern-day life stimulates compensatory food intake. Alongside the increase in food intake, increased industrialization and urbanization have resulted in increasingly sedentary lifestyles. Ultimately the resulting obesogenic environment makes it more challenging for individuals to maintain healthy body weight through lifestyle modifications.
An obesogenic environment in itself cannot lead to obesity. Ultimately it is our behaviour particularly regarding diet and exercise, which plays a fundamental role in the causation of obesity. Therefore, behavioural therapy is often a key part of the management of obese individuals.
Factors responsible for weight regain
Lifestyle modification, encompassing nutrition, physical activity and behavioural modification is the most commonly used strategy to help obese patients achieve and maintain weight loss. However, weight regain is the major limitation which mars the efficacy of this strategy for weight loss maintenance. Weight regain commonly occurs in patients who have lost weight by adopting lifestyle modification strategies, regardless of what dietary or behavioural intervention strategies have been used for weight loss.
Starvation defence response
It has been speculated that the body cannot distinguish between ‘dieting’ and ‘starvation’, and as such, the body’s first response to weight loss is to prevent adverse effects of starvation. Within 24 hrs of energy restriction, the body triggers ‘starvation defence response’. As a result, following weight loss, compensatory changes in biological pathways involved in appetite regulation, energy utilisation, and storage promote weight regain. Broadly, these compensatory changes include decreases in energy expenditure, fat oxidation, and anorexigenic hormones (e.g. leptin) levels and increases in orexigenic hormones (e.g. ghrelin), appetite and cravings. These physiological adaptations would have been advantageous for a lean person in an environment where food was scarce; however, in an environment in which energy-dense food is abundant and lifestyles are largely sedentary, it results in a high rate of relapse after weight loss. Activation of these compensatory mechanisms also supports the existence of an elevated body weight set-point in obese people, as discussed above.
Although a large proportion of obese individuals regain weight following weight loss, a proportion of individuals can successfully maintain a long-term weight loss. Further, those that do regain lost weight, do so at different rates. This may be largely explained by individual differences in genetic make-up, food environment and psychological factors.
Physiological adaptations to weight loss and factors favouring weight regain
Many clinicians and healthcare professionals engaged in weight management in individuals with obesity are not adequately aware of the reasons as to why is it so difficult to lose weight and keep it off. In the absence of this knowledge, they fail to provide effective biologically based interventions for this largely biologically-mediated disease. As stated above, apparently the body cannot distinguish between ‘dieting’ and ‘starvation’ and as such, irrespective of starting weight, caloric restriction triggers several biological adaptations designed to prevent starvation. These biological adaptations might be potent enough to undermine the long term effectiveness of lifestyle modification in most individuals with obesity, particularly in a ubiquitous obesogenic environment.
These mechanisms appear not to be part of a highly sensitive homeostatic feedback system designed to regulate body weight at any particular ‘setpoint’, instead, these mechanisms are triggered within 24 hrs of calorie restriction, i.e. before any weight loss, thereby suggesting that the so-called starvation defence response is activated in response to a reduction in calorie intake, rather than depletion of energy stores (fat stores). Importantly, these mechanisms operate irrespective of the adequacy of energy stores. Thus, these mechanisms may be more accurately described as anti-weight loss mechanisms rather than anti-starvation mechanisms per se.
In contrast, overfeeding results in fewer compensatory changes then food restriction, which induces compensatory changes in proportion to the degree of underfeeding. There is evidence to suggest that human biology evolved with a preference for energy intake and storage as compared to expenditure and it appears that these ‘regulatory’ mechanisms may reflect the same bias. Therefore it can be concluded that human beings are better adapted to protect against weight loss compared to weight gain, demonstrating the efficiency of food utilization, particularly when food resources are scarce. However, besides the biological adaptations designed to prevent starvation, additional biological adaptations occur with the development of obesity and these act to preserve or even increase an individuals highest sustained lifetime body weight.
The compensatory changes in biological pathways which encourage weight regain following weight loss encompass appetite regulation, energy utilization and storage. These changes affect our complex neuro-hormonal system that regulates energy homeostasis including perturbations in the levels of circulating appetite-related hormones and energy homeostasis, as well as alterations in nutrient metabolism and subjective appetite. Besides preadipocyte proliferation occurs increasing fat storage capacity. Besides, as discussed above, habituation to rewarding neural dopamine signalling develops with the chronic overconsumption of palatable foods, leading to a perceived reward deficit and compensatory increases in consumption. Some of these potential mechanisms which contribute to weight regain will be discussed here briefly.
However, it would be pertinent to emphasise here the significance of the necessary interaction between these biological pressures, genetic makeup and the obesogenic environment. Although nearly all obese and formerly obese individuals regain weight following behavioural weight loss, some do not. Further, those that do regain lost weight do so at different rates. This can mostly be explained by individual differences in genetic makeup and the obesogenic environment. However, a large number of psychological and social factors also contribute.
Appetite-related hormones have a key role in weight regain after weight loss and thus play a central role in weight loss maintenance. Except for pancreatic polypeptide, changes in hormones following weight loss tend to favour weight regain by increasing hunger and promoting energy storage.
Leptin – Leptin levels are reduced within 24 hours of energy restriction; more importantly, several studies have reported a greater reduction of leptin then would be expected for given losses of body fat. Reductions in leptin levels appear to trigger a starvation defence response, despite the persistence of abundant fat stores.
Other neuroendocrine changes – as discussed above, in addition to leptin, several hormones secreted from the gastrointestinal tract and adipose tissue have been implicated in the modulation of appetite, food intake, energy expenditure, and consequently body weight. For example, following diet-induced weight loss, there are increases in orexigenic hormones such as ghrelin and gastric inhibitory polypeptide and decreases in anorexigenic hormones, besides leptin, such as peptide YY, cholecystokinin, amylin, insulin and glucagon-like peptide-1. Thus weight loss could induce a simultaneous decrease in satiety and increase in hunger, potentially encouraging formerly obese individuals to overeat and regain lost weight.
More worryingly, findings from various studies have revealed that hormonal alterations in response to weight loss tend to persist long term. A study titled ‘Long-term Persistence of Hormonal Adaptations to Weight Loss’, published in the journal The New England Journal of Medicine in Oct 2011, enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. The study found that one year after initial weight reduction, the compensatory changes in the levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to baseline values, i.e. levels recorded before weight loss. Thus, these findings suggest that compensatory alterations in circulating mediators of appetite, which promote weight regain following a diet-induced weight loss, are not a transient response to weight loss. Findings from studies of obese and/or overweight individuals also suggest that after diet-induced weight reduction, weight regain is also associated with a disruption in the sensitivity to these hormones, especially leptin.
Bariatric surgery and adaptations in appetite-related hormones
However, in contrast to diet-induced weight loss, bariatric surgery has been shown to induce adaptations in the appetite-related hormones which favour weight-loss. The most common surgical options for extreme obesity include Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric banding. Gastric bypass surgery corrects obesity-induced changes in appetite-related hormone profiles and neural responsivity. Following gastric bypass surgery, levels of ghrelin are extremely low, while GLP-1 and PYY are elevated, which could attenuate appetite. These findings raise the possibility that the gastric bypass procedure reduces weight, at least in part, by altering the production and/or release of these mediators of appetite.
Besides its effects on appetite-related hormones, weight loss in obese individuals has been shown to affect various other neuroendocrine mechanisms, including mainly:
Thyroid hormones – weight loss in obese individuals has been shown to reduce thyroid hormone levels. As thyroid hormone is involved in increasing metabolic rate, reduction in thyroid hormone levels may contribute to simultaneous decreases in fat breakdown and increases in fat storage.
Hypothalamic-pituitary-adrenal (HPA) axis – Weight loss has been shown to increase HPA axis activity. As the HPA regulates stress-related elevations in cortisol, increases in this type of hormonal signalling can lead to increased appetite, fat accumulation and potentially, weight regain.
Catecholamine (epinephrine, norepinephrine) – Weight-suppressed obese individuals show lower levels of circulating epinephrine and norepinephrine which could compromise lipid oxidation. This shift in metabolic activity may encourage fat storage and weight regain.
Energy metabolism (energy balance)
Energy expenditure varies according to changes in body weight and the balance between ingested energy (in the form of calories in food) and ‘total daily energy expenditure’ (TDEE) is a fundamental determinant in the control of body weight. Loss of body weight following lifestyle modification results in the loss of both fat and lean mass. As discussed, reduction in body weight results in compensatory changes in energy expenditure, which tend to favour weight gain. The reduction in TDEE is a result of a reduction in REE (due to loss of metabolic tissue, i.e. both fat and lean mass), AEE (if less total mass must be moved during physical activity, the same activity will have less energetic cost, resulting in a decrease in AEE, if levels of physical activity are kept the same) and TEF (due to reduced food intake). This decrease in energy expenditure as a consequence of weight loss is known as ‘adaptive thermogenesis’ or ‘metabolic adaptation’ and it acts to counter weight loss and is thought to contribute to weight regain. Adaptive thermogenesis (AT) refers to fat-free mass (FFM)-independent decreases in energy expenditure.
However, a large number of studies have demonstrated that weight loss due to lifestyle modifications results in significantly greater reductions in resting and total energy expenditure than would be expected for given losses in the fat and lean mass. A study titled ‘Metabolic Slowing with Massive Weight Loss Despite Preservation of Fat-Free Mass’ published in The Journal of Clinical Endocrinology and Metabolism in Jul 2012, investigated body composition and energy expenditure in 16 severely obese (BMI 49.4 kg/m2) individuals competing in a nationally televised 30-week weight loss program of diet restriction and vigorous exercise. The study demonstrated a disproportionate slowing of REE during weight loss, despite relative preservation of fat-free mass. At 30 weeks, on average greater than one-third of the initial body weight had been lost, comprising 83% from fat and 17% from the fat-free mass. However, the REE reduced by 789 kcal/d, which was 504 kcal/d greater than expected, based on the change of body weight and composition.
This disproportionate reduction in energy expenditure, relative to body mass and composition, during weight loss maintenance, may be largely attributed to increases in the ‘skeletal muscle work efficiency’ (metabolic efficiency); an adaptation which takes place within 24 hrs of calorie restriction, before any loss of fat or lean mass. As a result of the metabolic adaptation, energy intake requirements during weight loss maintenance are lower than that of never obese individuals with the same BMI. Due to the higher metabolic efficiency, patients who achieve significant weight loss via lifestyle change will have to ingest up to 300 to 500 fewer (or burn up to 300 to 500 more) calories per day than someone of the same weight who never had obesity, just to maintain that weight. In other words weight-reduced, previously obese individuals are metabolically different from people who were never obese. To overcome this metabolic adaptation, obese individuals would need to continually reduce energy intake and maintain energy intake below that of never obese individuals at the same BMI. However, in the absence of a proportionately reduced energy intake, the persistence of this metabolic adaptation will predispose individuals to weight regain.
An additional theory points to changes in body composition that may result from the cycles of weight loss and regain, which most obese people go through. There is some evidence to suggest that the fat-to-lean ratio of mass regained during weight regain is higher than that of the mass lost initially during a weight loss diet. Simply stated when you regain weight after weight loss, the body regains less amount of lean mass and a higher amount of fat then it lost during weight loss, i.e. a proportion of lean mass is replaced with fat during the weight regain after weight loss. Thus, with each successive ‘weight-cycle’, the proportion of body fat begins to increase, in comparison to lean mass. As fat is metabolically less active compared to lean mass, increase in the fat-to-lean tissue ratio would lead to a decrease in metabolic rate (REE) and increase the propensity for weight gain. However, limited studies have been inconclusive in regards to weight cycling and enhanced weight regain.
Excess weight gain typically leads to changes in body composition, including significant alterations in adipose cellularity. The adipose tissue (fatty tissue) mass increases in two ways – hypertrophy, wherein the diameter of the fat cells increases, and hyperplasia, wherein the number of fat cells increases. To begin with, elevated body weight is generally associated with an increase in the diameter of fat cells (hypertrophy), as well as storage of greater amounts of fat within the fat cells. Most literature points to adipocyte hypertrophy as the main feature of obesity. However, as body fat increases, fat cells eventually reach a critical biological upper size limit, after which the enlarged fat cells secrete paracrine factors (factors produced by cells that then act on neighbouring cells in the same tissue) that induce preadipocyte (precursor cells derived from adipose tissue that can differentiate into adipocytes) proliferation. Thus, to begin with, excess calorie intake may lead to increases in fat cell size but subsequently increases in fat cell number largely determines the further gain in body weight. However, the preponderance of evidence suggests that hyperplasia occurs primarily in clinically severely obese individuals.
With lifestyle modification, when the body loses weight, the fat cell size decreases; however, the number of fat cells remains the same. Therefore, relative to individuals who have never been obese, weight-reduced (formerly) obese individuals, particularly clinically severely obese individuals, will have a significantly greater number of fat cells, which cannot be reduced via lifestyle modification. In other words, it can be said that weight loss in severely obese persons does not really “cure” their obesity, at least in terms of the number of fat cells. Liposuction is the only known treatment which can reduce the number of fat cells, but it has its complications.
Though, various potential mechanisms have been suggested in regard to the mechanisms via which the newly size-reduced fat cells encourage weight regain, however, it is not yet definitively known whether hyperplasia encourages weight regain in weight-reduced, formerly obese individuals.
Alterations in neural responsiveness
As discussed above, food intake is primarily mediated by two interactive neural systems, the homeostatic and reward-related (hedonic). An abundant supply of food in most industrialised societies has obviated the need for most homeostatic-driven eating. However, in response to calorie restriction, the homeostatic system serves to upregulate the reward-system to increase the perceived reward value of food, encouraging the consumption of more calorie-dense foods and weight regain. Besides, as discussed above, reward-related hedonic signalling easily overrides restrictive homeostatic and inhibitory signalling, driving increased food intake despite regulatory signal aimed at preventing excess calorie intake. This ‘overriding’ ability of the reward-related system demonstrates the same biological bias towards the intake and storage of energy, as discussed above. More importantly, it appears as though the neural propensity to consume more calorie-dense foods, as compared to low-calorie foods, persists after weight loss due to lifestyle modification and thus may contribute to weight regain.
Increase in reward-related responsiveness to food cues (include viewing or smelling of food stimuli, advertisements or any cues or situations associated with food-related memories) is seen within hours of caloric restriction and weight loss following lifestyle modification has been shown to increase the reward-related neural responsiveness to food cues. This increase in reward-related responsiveness, likely explains the commonly seen increased desire for “forbidden foods” in dieting individuals and illustrates a potential mechanism for the eventual loss of the dietary restraint and subsequent weight gain following weight loss due to lifestyle modification. Finally, these metabolic adaptations over time also remind us that the metabolic vulnerability of individuals with obesity persists even after their condition has supposedly been ‘cured’ by weight loss.
Addiction-like neural mechanisms
Above, under ‘food versus drugs’, I discussed how increased preference for, and consumption of, foods high in fat and sugar, had similarities with drug abuse. Recent evidence suggests that reduction in experienced reward also persists in weight-reduced formerly obese individuals, potentially contributing to weight regain. Food addiction has been reported to be associated with depression, negative affect (a personality variable that involves the experience of negative emotions and poor self-concept. Negative affectivity subsumes a variety of negative emotions, including anger, contempt, disgust, guilt, fear and nervousness), emotion dysregulation, eating disorder psychopathology, attention-deficit/hyperactivity disorder, and low self-esteem.
Neuroimaging methods such as fMRI have been used to elucidate the relation between neural reactivity and addictive-like behaviours; the studies have found that greater reactivity to food cues in the reward- and motivation-associated regions predicted greater future weight gain or a worse outcome in a weight loss program. Participants whose reward systems to foods are highly activated at the end of weight loss intervention are at risk of weight regain afterwards. Taken together, the above indicate that food addiction may exert an impact on weight loss and maintenance in the long-term, even though it has less effect on weight loss during the short-term. Therefore, it is important to assess food addiction at the end of the weight loss intervention, and for participants with a high score on food addiction scale, additional interventions to address the issue must be considered.
Psychological factors affecting weight regain
Despite the biological pressures on individuals to overeat to restore their original weight (i.e. set-point body weight) and living in an obesogenic environment, a proportion of individuals manage to continue to practice weight control behaviour and therefore maintain long-term weight loss. The answer to this central question, namely, why some individuals persist in practising weight-control behaviours, while others abandon it, has been provided by some research studies which have pointed to large differences in the psychological characteristics of the obese population seeking treatment.
A complex of cognitive factors and personality traits has been shown to influence complex eating and exercise behaviours involved in weight loss and maintenance of long-term weight loss:
Cognitive factors associated with weight loss
The two most influential cognitive factors associated with weight loss and weight loss maintenance are an increase in ‘dietary restraint‘ and a reduction in ‘disinhibition‘. Restraint and disinhibition play an important role in obesity status, diet quality, and on the psychopathology of disturbed and disordered eating behaviour. Dietary restraint is defined as the intention to restrict food intake in order to control body weight and shape, for instance, using small portions, avoiding fattening foods, and stopping eating before reaching satiation, in order to limit food intake. Disinhibition reflects a tendency towards overeating and eating opportunistically in an obesogenic environment, for example, eating in response to negative affect, being unable to resist food cues, and overeating in response to the palatability of food. The disinhibition is broadly of two types: internal disinhibition (i.e. eating in response to cognitive and emotional cues) and external disinhibition (i.e. eating in response to environmental cues).
A plausible reason for the association between cognitive factors and weight loss is that the increased dietary restraint and reduced disinhibition brought about by treatment could have led to weight loss via. decreased calorie intake. However, both these factors differ in their ability to reduce caloric intake and thereby bodyweight. While the impact of disinhibition on obesity is potent in increasing energy intake and susceptibility to disturbed eating, the action of cognitive restriction produces differential results, perhaps due to difficulty in maintaining cognitive control in an obesogenic environment replete with palatable foods. This complexity suggests that weight loss intervention should target reducing disinhibition, rather than increasing restraint. Besides, the differences in both these traits exist between men and women and over age categories. These differences are of consequence, particularly when designing interventions to combat obesity or disturbed and disordered eating behaviours, as these approaches may need to be more specifically tailored keeping in view the age and gender of the patient.
Cognitive factors associated with weight-loss maintenance
Satisfaction with the bodyweight achieved during treatment and confidence in their ability to lose additional weight without professional help are positively correlated with weight loss maintenance.
Personality traits and weight loss and weight loss maintenance
Personality traits are distinguishing qualities or characteristics that are the embodiment of an individual. They are your habitual patterns of behaviour, thoughts, and emotions that are relatively consistent and stable over the years and differ across individuals. By influencing behaviour they may play an important role in weight loss and weight loss maintenance. Among the various personality traits, ‘novelty-seeking’ is associated with obesity as well as with difficulty in losing weight. Novelty seeking is one of the defining characteristics of a ‘sensation-seeking’ personality in humans. It has been defined as “the seeking of novel sensations, and the willingness to take physical, social, legal and financial risks for the sake of such experiences.” High novelty-seeking scores indicate a strong appetite drive; as a result, binge eaters were found to score high on novelty seeking. Studies have shown that obese subjects who were successful in losing more than 10 per cent of their weight scored significantly lower on novelty-seeking than those who did not manage to lose that much weight; high scores in novelty-seeking are associated with less success in achieving behavioural therapy-induced weight loss.
Another aspect of personality ‘locus of control’, has also been shown to influence weight loss maintenance. Locus of control is the degree to which people believe that they have control over the outcome of events in their lives, as opposed to external forces beyond their control. Individuals with “internal locus of control” perceive they have control over the environment and feel they can control stimuli; in contrast, individuals with “external locus of control” perceive that their life is regulated by something outside their control. Individuals with an internal locus of control are more likely to lose weight and maintain weight loss without any external support, compared to individuals with an external locus of control. The concept of locus of control is intimately connected with self-efficacy discussed earlier.
Behavioural factors affecting weight regain
As discussed, behavioural strategies encompassing diet, exercise, and cognitive behavioural therapy are recommended for dynamic and sustained weight loss maintenance, either alone or in combination with pharmacotherapy. Though during the initial phase of intervention (typically ~ 6 months), behavioural approaches produce weight losses, on average, of approximately 8 kg (8%), participants tend to regain most of this weight loss over the next 3 – 5 years, with faster regains in earlier years. Some of the important behavioural factors which promote weight regain include:
Decreases in adherence to the prescribed regimens
Adherence to a prescribed behavioural regimen is critical to both initial and long-term weight loss. However, over time, adherence to behavioural changes that led to early weight loss tends to wane, largely due to increase in cost:benefit ratio. Initially, the positive outcomes of weight loss such as the sense of accomplishment and better fit of clothes outweigh the cognitive and physical efforts needed to lose weight. However, when the goal is to maintain weight loss, positive feedback is less compared to the effort required to keep adhering to the same regimen. Thus, the benefits no longer seem to justify the costs (that is efforts required to continue to adhere to the prescribed regimen).
An alternative explanation for the decline in adherence over time is that behaviours that led to the overweight/obese state in the first place, comprise a series of habits that have been formed over prolonged periods and these habitual behaviours return after a period of successful control.
There is a tremendous inter-individual variation in the weight loss outcomes with behavioural interventions and this variability increases during weight-loss maintenance. Evidently, behavioural approaches work more effectively for some individuals than for others; however, reasons for the same are not known.
As discussed above, long-term weight loss maintenance remains the main challenge of obesity treatment. Various studies have shown that this relapse has a strong physiological basis and is not simply the result of the voluntary resumption of old habits. Many clinicians and healthcare professionals engaged in weight management in individuals with obesity are not adequately aware of the reasons as to why is it so difficult to lose weight and keep it off. In the absence of this knowledge, they fail to provide effective biologically based interventions for this largely biologically-mediated disease. As sustained obesity is largely a biologically mediated disease, more biologically based interventions will be needed to counter the compensatory metabolic adaptations that maintain an individual’s highest lifetime body weight. Countering these responses to weight loss and the underlying adaptations that promote a positive energy imbalance could facilitate weight loss maintenance. In my next post, I shall discuss the various strategies to improve weight loss maintenance. However, before that I shall be addressing a vital question – Does obesity hit a point of no return?