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Appetite control and energy balance regulation in the modern world: Reward-driven brain overrides repletion signals

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Powerful biological mechanisms evolved to defend adequate nutrient supply and optimal levels of body weight/adiposity. Low levels of leptin indicating food deprivation and depleted fat stores have been identified as the strongest signals to induce adaptive biological actions such as increased energy intake and reduced energy expenditure. In concert with other signals from the gut and metabolically active tissues, low leptin levels trigger powerful activation of multiple peripheral and brain systems to restore energy balance. It is not just neurons in the arcuate nucleus, but many other brain systems involved in finding potential food sources, smelling and tasting food, and learning to maximize rewarding effects of foods, that are affected by low leptin. Food restriction and fat depletion thus lead to a 'hungry' brain, preoccupied with food. By contrast, because of less (adaptive thrifty fuel efficiency) or lost (lack of predators) evolutionary pressure, the upper limits of body weight/adiposity are not as strongly defended by high levels of leptin and other signals. The modern environment is characterized by the increased availability of large amounts of energy-dense foods and increased presence of powerful food cues, together with minimal physical procurement costs and a sedentary lifestyle. Much of these environmental influences affect cortico-limbic brain areas concerned with learning and memory, reward, mood and emotion. Common obesity results when individual predisposition to deal with a restrictive environment, as engraved by genetics, epigenetics and/or early life experience, is confronted with an environment of plenty. Therefore, increased adiposity in prone individuals should be seen as a normal physiological response to a changed environment, not in the pathology of the regulatory system. The first line of defense should ideally lie in modifications to the environment and lifestyle. However, as such modifications will be slow and incomplete, it is equally important to gain better insight into how the brain deals with environmental stimuli and to develop behavioral strategies to better cope with them. Clearly, alternative therapeutic strategies such as drugs and bariatric surgery should also be considered to prevent or treat this debilitating disease. It will be crucial to understand the functional crosstalk between neural systems responding to metabolic and environmental stimuli, i.e. crosstalk between hypothalamic and cortico-limbic circuitry.
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Appetite control and energy balance regulation in the modern
world: Reward-driven brain overrides repletion signals
Huiyuan Zheng, Natalie Lenard, Andrew Shin, and Hans-Rudolf Berthoud
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center Louisiana State
University System, Baton Rouge, Louisiana, USA
Abstract
Powerful biological mechanisms evolved to defend adequate nutrient supply and optimal levels of
body weight/adiposity. Low levels of leptin indicating food deprivation and depleted fat stores have
been identified as the strongest signals to induce adaptive biological actions such as increased energy
intake and reduced energy expenditure. In concert with other signals from the gut and metabolically
active tissues, low leptin levels trigger powerful activation of multiple peripheral and brain systems
to restore energy balance. It is not just neurons in the arcuate nucleus, but many other brain systems
involved in finding potential food sources, smelling and tasting food, and learning to maximize
rewarding effects of foods, that are affected by low leptin. Food restriction and fat depletion thus
lead to a “hungry” brain, preoccupied with food. In contrast, because of less (adaptive thrifty fuel
efficiency) or lost (lack of predators) evolutionary pressure, upper limits of body weight/adiposity
are not as strongly defended by high levels of leptin and other signals. The modern environment is
characterized by increased availability of large amounts of energy dense foods and increased presence
of powerful food cues, together with minimal physical procurement costs and a sedentary lifestyle.
Much of these environmental influences impact cortico-limbic brain areas concerned with learning
and memory, reward, mood, and emotion. Common obesity results when individual predisposition
to deal with a restrictive environment as engraved by genetics, epigenetics, and/or early life
experience, is confronted with an environment of plenty. Therefore, increased adiposity in prone
individuals should be seen as a normal physiological response to a changed environment, not in
pathology of the regulatory system. The first line of defense should ideally lie in modifications to
the environment and lifestyle. However, because such modifications will be slow and incomplete, it
is equally important to gain better insight how the brain deals with environmental stimuli and to
develop behavioral strategies to better cope with them. Clearly, alternative therapeutic strategies such
as drugs and bariatric surgery should also be considered to prevent or treat this debilitating disease.
It will be crucial to understand the functional crosstalk between neural systems responding to
metabolic and environmental stimuli, i.e. crosstalk between hypothalamic and cortico-limbic
circuitry.
Keywords
Neural control of appetite; metabolic need; internal depletion signals; environmental food cues;
cortico-limbic systems; food reward; leptin; obesity
Corresponding author: Hans-Rudolf Berthoud Pennington Biomedical Research Center Neurobiology of Nutrition Laboratory 6400
Perkins Road Baton Rouge, LA 70808 Ph: 225-763-2688 Fax: 225-763-0260 berthohr@pbrc.edu.
NIH Public Access
Author Manuscript
Int J Obes (Lond). Author manuscript; available in PMC 2010 March 15.
Published in final edited form as:
Int J Obes (Lond). 2009 June ; 33(Suppl 2): S8–13. doi:10.1038/ijo.2009.65.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Introduction
The obesity epidemic continues unabated with no cure in sight. By increasingly affecting
children and adolescents it is threatening to roll back much of the significant progress made in
developed countries during the last century in living healthy and independent lives and in
creating social harmony and economic productivity. The discovery of leptin over a decade ago
spawned great hope for an end to the obesity crisis, like the discovery of insulin essentially
cured type 1 diabetes half a century ago. That this has not happened, at least not yet, has been
the subject of great debate. How is it possible that the ostensibly perfect negative feedback
signal regulating adiposity permits accumulation of excessive body fat in the first place and
why does leptin treatment not reverse obesity?
In this brief review, we will argue that the inherent asymmetry in the adaptive response to
famine and feast may be responsible for the fact that simply changing the food environment
can push adiposity of a population upwards and result in increased prevalence of obesity. We
will review the emerging literature showing that low leptin together with other hormones and
metabolites signaling relative decreases in nutrient supply powerfully invoke neural
mechanisms of reward, motivation, and decision-making, and how this is exploited by the
modern environment and lifestyle. We will argue that homeostatic defense of the upper limits
of adiposity are inherently weakened by genetic predisposition and/or rapid and reversible
development of resistance to metabolic feedback signals such as leptin. Finally, we will outline
the distributed neural systems involved in appetite control and energy balance regulation and
highlight the importance of crosstalk between the systems traditionally linked to metabolic
regulation and processing of cognition, reward, and emotions.
Strong defense of adequate nutrition and the lower limits of adiposity
Procurement and availability of sufficient energy and essential nutrients is defended by a
complex system consisting of fail-save, redundant pathways (1,2). Larger animals, including
humans, can endure considerable periods without food by burning fat stored in significant
depots and reducing energy expenditure. Smaller animals often do not have significant fat
stores and fall into torpor for survival. In either case, hunger is strongly expressed at least
initially. To organize these life-saving responses we rely on accurate sensors of the internal
milieu and the external world, flexible and adaptive integrators that make sense out of all this
diverse input, and powerful effectors that act both on the input and output arms of energy
balance. The coordinator of this concerted effort to prevent nutrient depletion and restore
energy supply is the brain. Food restriction and fat depletion lead to a “hungry” brain,
preoccupied with food.
Research efforts in the post-leptin discovery era have mainly focused on the “metabolic brain”,
identifying some of the crucial neural circuits in hypothalamus and hindbrain. Clearly, the
hypothalamic neurocircuitry is crucial for body energy homeostasis as indicated by the
development of obesity or leanness after loss or gain of function manipulations of its main
components [e.g. (3)]. It is now thought that the mediobasal hypothalamus is the main hub for
sensing availability of nutrients and for generating an integrated adaptive response to deviations
from adiposity levels that are appropriate for a set of given internal and external conditions
(4,5). Although this circuit is assumed by many to regulate body weight and adiposity within
a narrow set point, much like a thermostat controls room temperature, this view has been largely
abandoned in favor of a more flexible regulator that can learn from past experience and adapt
to changing environmental factors (floating set point). Arguably, the major force “designing”
the system was the constant struggle throughout evolution to find enough food for survival,
resulting in a very strong defense of the lower limits of adiposity.
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However, to understand how metabolic need is translated into strong behavioral actions that
successfully compete with other motivated behavior, the role of the “cognitive and emotional
brain” can no longer be neglected.
Cortico-limbic pathways coordinate metabolic need with the external world
It is clear that the neurocircuitry originating from the primary energy sensors in the arcuate
nucleus described above is embedded in a much larger neural system that allows adaptation
and coordination of metabolic needs to the demands and intricacies of the prevailing
environment. For example, it does not make sense for the hungry vole to leave the burrow if
the weasel waits outside. In fact, much of the brain has evolved to take care of hunger ever
since mobile life forms emerged. Although procuring food in our modern environment is no
longer difficult or potentially hazardous, it used to be a demanding task for most of the last 5
million years. Even more primitive invertebrate animals such as honey bees and ants use
elaborate navigation and communication strategies to secure food sources and guarantee
survival for the individual as well as society (6-8).
We remember past experiences with foods, particularly if the experience was out of the
ordinary. A growing number of studies suggest that representations of experience with foods
are generated in the orbitofrontal cortex, an area in the prefrontal cortex that receives
converging information through all sensory modalities (9). Therefore, representations contain
a number of sensory attributes, including shape, color, taste, and flavor, as well as links to time,
location, social context, cost, and reward expectation (9,10). The orbitofrontal cortex is in
intimate contact with other cortical areas, particularly the anterior cingulate, perirhinal and
entorhinal cortices, as well as with the hippocampal formation and the amygdala, often
collectively referred to as paralimbic cortex [for review see (9)]. It is within these areas that
polymodal representations are thought to be available as working memory for constant
updating.
A strong basic drive or motivation was necessary to leave the safety of a burrow or cave and
procure nutrients in a dangerous environment with predators and toxic plants. Emotions
evolved as a mechanism to reinforce beneficial and suppress potentially harmful stimuli and
behaviors. For example, the sweet taste of certain foods and the process of satiation are
associated with positive emotions that augment the motivational drive to find food and eat.
Similar to sexual pleasure, the feelings of satisfaction and well being generated by eating result
in strong motivation to engage in these behaviors again. The reward value of a particular food
is bundled with the other attributes into the stored representations discussed above. Thus, life
is all about learning how specific behavioral responses or actions lead to positive emotions or
reward in the future.
An expanded view of energy homeostasis
It was originally thought that the classic nutritional feedback signals such as leptin, insulin,
gut hormones, and circulating nutrients themselves, act mainly on a few areas of the brain such
as specific parts of the hypothalamus and brainstem. However, recent studies suggest that these
metabolic signals have a much broader influence on brain functions.
For example, leptin has been shown to modulate food-related sensory input signals of all
modalities even at early stages of processing, so that low leptin levels can dramatically lower
detection thresholds of external stimuli signaling availability of nutrients (11-14). Leptin and
insulin can also act directly on mesolimbic dopamine neurons to modulate ‘wanting’ of food
(15-17). Neural activity in the nucleus accumbens elicited by visual food stimuli is very high
in genetically leptin-deficient adolescents and promptly returns to normal levels upon leptin
administration. While in the leptin deficient state, nucleus accumbens activation was positively
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correlated with ratings of liking in both the fasted and fed state, it was correlated only in the
fasted state after leptin treatment and in normal individuals (18). The lower gut hormone PYY
(3-36), which has now been convincingly demonstrated to suppress food intake in humans and
rodents(19), also modulates activity of the ventral tegmental area (VTA) and ventral striatum
(20). In contrast to leptin, the gut hormone ghrelin appears to facilitate foraging behavior and
increase reward processing as part of its orexigenic action (21-25).
Dieting in overweight or obese humans has a very high failure rate, with most of them
developing strong food cravings and inevitable relapse. The mechanisms of this paradoxical
behavior have not been clear. The homeostatic regulatory system could be expected to
cooperate in voluntary weight loss not make it difficult. However, comparing brain activity
changes elicited by visual food stimuli in obese subjects before and after losing 10% body
weight through dieting revealed the anatomy of a “hungry” brain. It is important to note that
after a 10% weight loss these individuals were still obese with lots of excess adipose tissue.
Still, looking at pictures of food evoked much larger changes in brain activity after this
moderate weight loss. Although activity changes were found in the traditional homeostatic
areas of hypothalamus and brainstem, many cortico-limbic areas involved in cognitive and
emotional functions were most strongly affected by the weight loss (26). Importantly, most of
these changes were fully reversed after leptin administration, and leptin treatment during
dieting increased the chance to reach the weight loss goal and prevent relapse in another cohort
of obese patients (27).
Thus, the traditional view of neural circuits regulating energy homeostasis has been expanded
to include neural mechanisms of learning and memory, reward, attention, decision-making,
mood, and emotionality. Adequate supply of energy is simply too important as not to include
these powerful neural processes. To distinguish eating driven by internal, metabolic hunger
signals from eating driven by hedonic, environmental signals in the absence of metabolic need,
the terms “homeostatic” and “non-homeostatic” controls of appetite have recently been adopted
(28-31). In light of the intimate neural interactions between these two classes of signals, this
distinction may have been premature. Metabolic signals can modulate the cortico-limbic
systems involved in higher brain functions, and the cortico-limbic systems can hijack the
behavioral/metabolic effector mechanisms controlling energy balance. Together they serve one
purpose – to maintain an optimal internal millieu in harmony with the external world.
Why does feedback from nutrient repletion signals not prevent obesity?
Weak defense of the upper limits of body weight
Evolutionary pressure has also existed to defend the upper limits of adiposity and, perhaps
more likely, body weight (32). Disadvantages of elevated body weight are evident in the
relationship between prey and predator – a heavier rodent is more likely to become prey of a
weasel or bird compared to a lean rodent. Humans too were prey of larger predators, but the
selection pressure for leanness disappeared with the use of weapons, fire, and shelter. The loss
of selection pressure allowed the upper boundaries of adiposity and body weight to drift
upwards by random genetic mutations over the last 2 million years or so (32).
Natural resistance to negative feedback signals
We now know that in most humans, obesity is a state of leptin resistance with high circulating
leptin levels, and the finding that very few obese patients respond favorably to exogenous leptin
was a major disappointment (33,34). Animal studies have shown that the same thing happens
to laboratory rats and mice, domesticated animals like cats and dogs, as well as wild animals
like polar bears and baboons, when they are exposed to human-like diets high in fat, sugar, and
energy (35,36). Therefore, in contradiction to all the body weight set point and adipostat
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theories positing leptin as the key negative feedback signal, slowly increasing circulating leptin
levels do not prevent development of obesity in many individuals. Rises in other anorexigenic
hormones such as insulin and amylin, as well as metabolites such as glucose and fatty acids
are also not doing their expected job, and neither do decreases in the orexigenic gut hormone
ghrelin. If prone individuals are exposed to the modern environment, the energy balance system
simply equilibrates at a new higher level of body weight/adiposity, completely disregarding
absolute values of feedback signals. This suggests that there is no predetermined set point for
body weight/adiposity regulation, but that body weight/adiposity is defended within a range
that depends on environmental conditions and individual predisposition.
Dependence of body weight/adiposity on environmental conditions should not be too
surprising, as it makes a lot of sense for an organism to store extra energy for a rainy day. This
is illustrated in seasonal animals, where leptin is ineffective in curbing appetite during summer,
when food is abundant (37). The modern human environment could thus be regarded as the
equivalent of continuous “summer” with natural leptin resistance. Before the modern era, this
“summer” used to be broken by winters and famines that quickly restored leptin sensitivity.
This seems to be confirmed by better success with leptin-treatment when it is given as an
adjunct to moderate food intake restriction (27,38). A state of natural leptin resistance may be
accomplished by increased expression of negative modulators of leptin receptor signaling.
These intracellular signaling molecules could act as rapid molecular switches to turn leptin
sensitivity on and off, depending on a particular combination of internal and external factors.
The modern environment acts on cortico-limbic systems to over-stimulate food intake
The major direct environmental factors thought to contribute to increased energy intake are
availability, portion size, energy density, palatability, variety, and presence of food cues. Other
important factors indirectly leading to poor food choice and overeating can be found in
agricultural policies, pricing strategies, socioeconomic status, level of education, and stress
vulnerability. The potential obesogenic role of many of these factors and recommendations for
dealing with them have been reviewed recently [e.g. (39,40)]and will not be further discussed
here.
While there has been a flood of studies demonstrating the acute food intake stimulatory effects
of such environmental factors [e.g. (41,42)], or correlations of exposure to such factors with
body mass index (43), few controlled interventional studies have demonstrated cumulative
effects on food intake and increases in body weight by selectively changing one of these factors.
In one such controlled clinical study, it was shown that increased portion size leads to
significantly increased energy intake and weight gain over a period of 11 days (44). Many more
such studies will be necessary to determine the relative importance of each factor and the
capacity to interact with other factors in specific populations. However, it is already quite clear
that the modern food environment has changed, and promotes increased energy intake and
sedentary behavior.
The modern environment primarily impinges on higher brain functions such as learning and
memory, reward optimization, attention, planning, and execution, organized mainly in cortico-
limbic circuits. As discussed above, these brain systems are essential for efficient food
procurement and they are specifically targeted by the advertising industry (45-47). As shown
by using subliminal stimuli, such processes of memory formation and recall, reward evaluation,
and preparation for motivated actions often take place outside awareness and thus partially
escape conscious executive control (48,49).
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Conclusions
The relative ineffectiveness of current pharmacological and dietary approaches to prevent or
reverse obesity makes sense when considering the complex and redundant neural systems
conferring the strong basic drive to eat. The lower level of body weight/adiposity is staunchly
defended. Low leptin and other signals resulting from inadequate nutrient reserves turn the
brain rapidly into a “hungry machine”. The slightest relative drop in customary nutrient
availability, even at elevated body weight levels, triggers a powerful response. On the other
hand, the upper level of body weight is only poorly defended, particularly in genetically prone
individuals. This asymmetric response pattern in which the “eat more” command is dominant
over the “stop eating” command inevitably leads to slow and incremental weight gain. Not
unlike the ratcheting action of a car jack, exposure to the environment of plenty pushes body
weight only in one direction - upwards.
Realizing that in this scenario, the primary cause of obesity is seen in changes in environmental
and lifestyle changes, prevention and treatment therapies should first focus on reversing or
modifying some of the most salient changes. Secondly, understanding the neural mechanisms
translating environmental stimuli into behavioral actions will be crucial for the development
of behavioral modification and pharmacological intervention therapies. Finally, development
of pharmacological or surgical tools bolstering existing internal feedback signals or enhancing
their downstream signaling capacity should also be continued.
Acknowledgments
Supported by National Institute of Health DK071082
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Zheng et al. Page 8
Int J Obes (Lond). Author manuscript; available in PMC 2010 March 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Fig. 1.
Schematic diagram showing major factors determining food intake and energy balance in
restrictive and modern environments. The availability of nutrients (internal millieu) is detected
by a plethora of distributed sensors and controls food intake directly through classical
hypothalamic-brainstem pathways and indirectly through modulation of food reward processes
in cortico-limbic structures (blue arrows). Low nutrient availability as, for example, signaled
by low leptin levels, produces very strong sensitization of cognitive and hedonic mechanisms
enabling procurement and ingestion of food as well as generating high reward and satisfaction.
This system evolved in order to guarantee adequate nutrient supply in restrictive environments
requiring a high physical activity level. The modern environment and lifestyle are characterized
by high food availability, abundant food cues, and high food palatability (red arrows), all
enhancing food intake either directly or through the same cortico-limbic systems easily
sensitized by nutrient depletion signals. In addition, the built environment, sedentary lifestyle,
and low procurement costs lead to decreased physical activity and in turn, increased nutrient
availability (green arrows). Obesity develops in prone individuals that either efficiently
translate exaggerated hedonic, cognitive, and/or emotional pressure exerted by the modern
environment and lifestyle into increased eating, or individuals in which energy repletion signals
are not able to suppress hedonic eating, or both.
Zheng et al. Page 9
Int J Obes (Lond). Author manuscript; available in PMC 2010 March 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
... Despite that the only two long-term studies reported no differences between HIIT/SIT and MICT after 12-week interventions (Martins et al., 2017;Sim, Wallman, Fairchild, & Guelfi, 2015), more studies are needed to make conclusions on the long-term impact of the intensity and exercise modality. Lastly, to comprehensively examine the effects of HIIT/SIT on appetite sensations, alterations in eating behavior, for example, food preferences or selection of specific nutrients and tastes, should be taken into consideration (King et al., 1997;Zheng, Lenard, Shin, & Berthoud, 2009). Nevertheless, in one of the included studies that reported the desire to eat specific foods along with other more frequently analyzed parameters of appetite sensations (e.g., hunger), no significant differences were found between a bout of HIIT and MICT (Panissa et al., 2019). ...
Article
Background: Exercise intensity has been suggested to influence acute appetite-regulating gut hormone responses after exercise. High intensity interval training (HIIT) with near maximal to maximal intensity or sprint interval training (SIT) with supramaximal intensity might induce greater effects on gut hormones compared to moderate intensity continuous training (MICT), while current findings were inconsistent regarding the effects of these popular training methods. Objective: This systematic review and meta-analysis aimed to synthesis the findings in the literature and explore the impact of exercise modality on acylated ghrelin (AG), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Methods: After searching the major databases (PubMed, Web of science and ScienceDirect, Scopus, Cochrane Library) to find articles published up to May 2022, twelve studies that compared hormone responses to HIIT/SIT and MICT were identified and included in the analysis. Results: A random-effects meta-analysis showed that HIIT/SIT and MICT decreased AG concentration and increased GLP-1 and PYY concentration compared with no exercise control group, while interval training protocols, especially SIT protocols, elicited greater effect sizes in suppressing AG levels at all of the analysed time points and PYY immediately post-exercise compared to MICT. Conclusion: Acute SIT with lower exercise volume appears to be a more advantageous approach to decrease plasma AG concentration and potentially suppress hunger to a greater extent compared to MICT, despite the similar effects of HIIT/SIT compared to MICT in increasing anorectic hormones (i.e., GLP-1 and PYY). Future studies are needed to further investigate the impact of moderators (e.g., gender, body composition and exercise mode) on the variability of changes in gut hormones after interval trainings.
... Despite that the only two long-term studies reported no differences between HIIT/SIT and MICT after 12-week interventions (Martins et al., 2017;Sim, Wallman, Fairchild, & Guelfi, 2015), more studies are needed to make conclusions on the long-term impact of the intensity and exercise modality. Lastly, to comprehensively examine the effects of HIIT/SIT on appetite sensations, alterations in eating behavior, for example, food preferences or selection of specific nutrients and tastes, should be taken into consideration (King et al., 1997;Zheng, Lenard, Shin, & Berthoud, 2009). Nevertheless, in one of the included studies that reported the desire to eat specific foods along with other more frequently analyzed parameters of appetite sensations (e.g., hunger), no significant differences were found between a bout of HIIT and MICT (Panissa et al., 2019). ...
Article
Interval training protocols have gained popularity over the years, but their impact on appetite sensation compared to officially recommended training method, moderate intensity continuous training (MICT) is not well understood. Thus, this systematic review and meta-analysis aimed to compare a single session of high intensity interval training (HIIT) including sprint interval training (SIT) with MICT on appetite perception measured by the visual analog scale (VAS). After searching up articles published up to September 2021, 13 randomized controlled studies were included in the meta-analysis. Outcomes of meta-analysis demonstrated that both acute sessions of HIIT/SIT and MICT suppressed appetite compared to no-exercise control groups immediately post exercise but there were no significant effects 30-90 min post exercise or in AUC values, indicating a transient effect of exercise on appetite sensations. Moreover, differences in appetite sensations between HIIT/SIT and MICT were negligible immediately post exercise, but HIIT/SIT suppressed hunger (MD = -6.347 [-12.054, -0.639], p = 0.029) to a greater extent than MICT 30- to 90-min post exercise, while there was a lack of consistency other VAS subscales of appetite. More studies that address the impact of exercising timing, nutrient compositions of EI and differences in participants' characteristics and long-term studies analyzing chronic effects were needed to comprehensively examine the differences between HIIT/SIT and MICT on appetite and EI. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/PROSPERO], Identifier [CRD42021284898].
... /2022 6 One of the many factors influencing food intake that has not yet been targeted by the pharmaceutical industry is sensory information/processing. A large amount of sensory information from both the oronasal cavity and gastrointestinal tract is sent to the central nervous system (CNS), imparting information related to macronutrient composition, caloric density, osmolarity, and potential toxicity of food (Ahima & Antwi, 2008;Concas, et al., 2022;Morrison & Berthoud, 2007;Saper, Chou, & Elmquist, 2002;Zheng, Lenard, Shin, & Berthoud, 2009). Indeed, it is the sense of taste which acts to protect the rest of the alimentary canal by providing information on which nutrients to ingest and which to reject (Concas, et al., 2022;Forde & de Graaf, 2022;Mattes, 2003;Scott & Verhagen, 2000;Tanaka, Reed, & Ordovas, 2007). ...
Preprint
The availability of high-calorie foods is likely a causative factor for high rates of obesity and metabolic disorders, which have been linked to food intake dysregulation. Several gut peptides have been implicated in feeding modulation and body mass accumulation. For example, glucagon peptide-like 1 (GLP-1) and peptide tyrosine-tyrosine (PYY) have been shown to mediate satiety and reduce food intake. While systemic administration of such peptides has been explored as a therapy for metabolic disease, the effects of these hormones on taste signaling should also be considered given the importance of taste to feeding decisions. Peptide signaling systems are present in taste buds and oral GLP-1 and PYY signaling has been shown to influence taste responsiveness and feeding. Indeed, we previously demonstrated that genetic knockout of PYY in mice can impact on taste responsiveness and feeding and that viral overexpression of PYY in the salivary glands of these mice can rescue responsiveness. The present work uses AAV-mediated salivary gland treatment of both GLP-1 receptor agonist exendin-4 and PYY encoding vectors to explore the impact of the presence of these peptides on taste and body-mass accumulation in wild-type mice with intact peptide signaling systems. Results showed a significant effect of salivary gland treatment on responsiveness to multiple taste qualities. Treatment with a vector designed to overexpress both peptides in saliva resulted in substantial reduction in body mass accumulation. These findings show taste modulation and impacts on body mass accumulation by the targeting of salivary glands with vectors designed to overexpress metabolic peptides in wild-type mice and suggest that the taste bud is a promising substrate for food intake modulation.
... Paediatric and adolescent obesity is a particularly important context in which to improve adherence due to the evidence that highlights neurobiological and hormonal responses to weight loss which serve to protect one's highest weight [9][10][11]. That is, with the accumulation of adopsites, there are neurohormonal changes (proinflammatory markers) that alter the appetite system in favour of overconsumption and alter the response to weight loss to favour regain. ...
Article
Full-text available
Obesity is a chronic disease, in which treatment outcomes are highly dependent on patient and family adherence to behavioural recommendations. The role of healthy eating, physical activity, medication adherence as well as adherence to pre- and post-bariatric surgery protocols are of utmost importance for long-term treatment outcomes. Even the best interventions are not likely to reach their maximum benefit without significant levels of adherence on the part of the individual and family. Traditionally, the annual meeting of the European Childhood Obesity Group (ECOG) includes an expert workshop addressing one specific topic within the field of childhood obesity. During the 30th annual meeting, hosted by the University of Pécs, Hungary, as a virtual meeting, “adherence to treatment recommendations in obesity as a chronic disease” was addressed. The discussions that developed during the workshop are summarized in the following article.
... Phytochemicals are the compounds produced by plants such as carotenoids, triterpenes and polyphenols (flavones, flavonoid, flavonols, phenolic acids, curcuminoids, stilbenes and anthocyanins) and possess antioxidative, antiadiposity and cardioprotective activities. Certain phytochemicals act as thermogenic compounds including caffeine, salicylic acid, ephedrine and capsaicin, and prevent excessive accumulation of fats in body tissues by burning extra calories (Zheng et al. 2009). ...
Chapter
The endocrine system comprises of glands secreting different hormones directly into the blood stream. Basically the hormones reach almost every cell and this communication is slower than the nerve communication, but is more persistent. Other than endocrine glands, additional sources of hormones are also present in the body such as prostaglandins are produced and secreted from plasma membranous phospholipids of many cells. Some prostaglandins are responsible for causing pain and inflammation, especially in case of arthritis, while some others show their actions with pituitary hormone oxytocin to cause uterine contractions during childbirth. Some organs produce specific hormones such as intestine (cholecystokinin, secretin, and gastrin), liver (hepcidin, insulin-like growth factor, and thrombopoetin), kidney (angiotensin, renin, and erythropoietin) and even the heart (atrial natriuretic peptide). The major endocrine glands, including the pituitary, thyroid and parathyroid glands, pancreas, adrenal glands and the reproductive organs (ovaries and testes) are represented in Figure 1. All the endocrine glands are interconnected with one another and secrete different hormones for regulation of homeostasis, growth and development, and metabolism and reproduction in the body by direct transmitting messages to the target organ receptors. To keep the balance in hormonal levels, complex feedback system is present, working in form of positive and negative feedback mechanisms to control the secretion of hormones (Shier et al. 2007).
Chapter
A nutrição é uma característica inerente à vida. A aquisição de matéria-prima proveniente do meio ambiente é considerado fator imprescindível para a existência dos mais variados seres, dos unicelulares, mais simples, aos pluricelulares, mais complexos. Assim o fenômeno da vida e o da nutrição são, reciprocamente, codependentes. Os elementos essenciais e a energia necessários para manter as atividades mais primordiais do organismo vivo estão presentes nos alimentos. Estes devem atender às demandas dos tecidos vivos tais como de crescimento, manutenção, restauração e trabalho. Nos alimentos encontram-se os nutrientes, seus constituintes químicos mais simples, tais como carboidratos, lipídios e proteínas (macronutrientes – fornecedores de energia metabólica); sais minerais e vitaminas (micronutrientes – elementos reguladores); e também a água. Todos estes, em conjunto, apresentam relevante papel nos mais diversos eventos biológicos como regulação das reações orgânicas, síntese de moléculas, crescimento, desenvolvimento e reparo de tecidos, entre outros. O sistema nervoso exerce a função integradora e de comando sobre os outros sistemas fisiológicos, favorecendo o dinamismo homeostático que o nosso organismo necessita para estar vivo. Assim o sistema nervoso é originado, desenvolve-se, passa pelo processo de maturação, pode modificar-se com a capacidade de reorganizar-se ao longo da vida, envelhece, degenera e morre. Essa capacidade de modificar-se, tanto morfologicamente como funcionalmente, é conhecida como plasticidade e proporciona ao organismo a adaptação ao meio em que vive. Alguns fatores externos, como a nutrição, influenciam diretamente os processos de desenvolvimento e são vitais para guiar toda a organização, estrutura, função e metabolismo do sistema nervoso. No decorrer do capítulo iremos correlacionar os processos de formação, desenvolvimento e crescimento, que envolvem os aspectos morfofuncionais das células neurais com nutrição adequada, utilização de nutrientes, durante os períodos pré e pós-natal, infância, adolescência e envelhecimento do sistema nervoso. Ressaltaremos as alterações da nutrição inadequada na fase precoce da vida, a qual pode interferir na plasticidade neural, modificando características fenotípicas do sistema nervoso maduro.
Chapter
No decorrer da evolução da humanidade, observamos mudanças no comportamento de ingestão dos alimentos. Antes, havia um maior consumo de alimentos naturais, ricos em nutrientes. Contudo, atualmente, após a evolução industrial, houve uma mudança no padrão de vida das pessoas e, associada a isso, verifica-se também uma alteração nos hábitos alimentares. Hoje em dia, as pessoas ingerem muito mais alimentos processados, pobres em nutrientes, rápidos e de fácil ingestão. Nas fases iniciais da vida, durante o período crítico do desenvolvimento, muitas crianças consomem predominantemente alimentos tipo fast food. Dessa forma, podem comprometer o seu desenvolvimento craniofacial e, por conseguinte, funções básicas para o comportamento alimentar, como a mastigação e a deglutição. Tais atos motores são funções vitais para o ser humano, e agem de forma sincrônica, haja vista que a mastigação prepara o alimento para a deglutição. Tanto a mastigação como a deglutição são de extrema importância para a nutrição, já que controlam, direta ou indiretamente, os mecanismos de apetite e saciedade. Ademais, as características dos alimentos, a exemplo da textura, do sabor e do odor, podem interferir na dinâmica das supracitadas funções motoras, podendo interferir no tempo de trânsito dos alimentos, controlando, assim, o tamanho e a duração das refeições. Portanto, no decorrer deste capítulo, abordaremos os conceitos e o processamento básico do alimento durante a mastigação e a deglutição, além de como ocorre o seu desenvolvimento e como se processa durante o envelhecimento. Ressaltaremos também a importância das mencionadas funções motoras para a nutrição, abordando a influência das características dos alimentos sobre tais funções motoras. E, por último, destacaremos o efeito da manipulação nutricional, sobretudo da desnutrição, sobre a mastigação e a deglutição.
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Bei Patient*innen mit Binge-Eating-Störung (BES) kommt es zu wiederkehrenden Episoden, in denen sie in kurzer Zeit große Mengen an Nahrungsmitteln zu sich nehmen. Dies passiert insbesondere dann, wenn sie sich in einer negativen Stimmungslage befinden. Die Mechanismen dieses Stimmungseffekts auf das Essverhalten sind jedoch bisher kaum erforscht worden. In dieser Studie werden die Auswirkungen negativer und neutraler Stimmungszustände auf implizite Annäherungsund Vermeidungstendenzen gegenüber Nahrungsmittelreizen bei Patient*innen mit BES im Vergleich zu Kontrollpersonen untersucht. Konkret wurden Teilnehmende mit diagnostizierter BES und Adipositas (n = 40), Personen mit Adipositas ohne Essstörungssymptomatik (n = 40) und gesunde Kontrollpersonen (n = 29) in einer computergestützten Aufgabe gebeten, sich Bildern von kalorienreichen und kalorienarmen Lebensmitteln mittels der Bewegung einer Computermaus zu nähern ("heranziehen") oder sie zu meiden ("wegdrücken"). Die Testung erfolgte, nachdem eine negative oder neutrale Stimmungslage induziert worden war. Patient*innen mit BES zeigten unter neutralen Stimmungsbedingungen eine Vermeidungsneigung. Eine Kontrastanalyse bestätigte jedoch, dass eine negative Stimmung die Annäherungstendenzen bei adipösen BES-Patient*innen erhöhte. Bei den Gruppen der adipösen Personen ohne Essstörung oder der gesunden Kontrollpersonen zeigte die induzierte traurige Stimmung dagegen keinen Effekt. Die Stimmung wirkte sich auch nicht auf die von den BES-Patient*innen selbst angegebene Bewertung des Drangs zum Verzehr von Lebensmitteln aus. Diese Ergebnisse haben Auswirkungen auf das Verständnis des Zusammenspiels zwischen Stimmungszuständen und Essanfällen sowie auf die Entwicklung von Behandlungsansätzen.
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Adiponectin and leptin are important mediators of metabolic homeostasis. The actions of these adipokines extend beyond adipocytes and include systemic modulation of lipid and glucose metabolism, nutrient flux, and the immune response to changes in nutrition. Herein, we hypothesized that short-term intervention with a vegan diet might result in an improvement of plasma concentrations of adiponectin and leptin and the leptin/adiponectin ratio. We investigated the response of plasma adiponectin and leptin to a 4-week intervention with a vegan or meat-rich diet and its associations with sex, BMI and nutritional intake. Fifty-three healthy, omnivore participants (62% female, average age 31 years and BMI 23.1 kg/m2) were randomly assigned to a vegan or meat-rich diet for 4 weeks. Plasma adiponectin and leptin were lower in men compared to women both at the beginning and end of the trial. The concentration of adiponectin in women was significantly higher both when comparing their transition from omnivorous to vegan diet (p = 0.023) and also for vegan versus meat-rich diet at the end of the trial (p = 0.001), whereas plasma leptin did not vary significantly. No changes in adiponectin were identified in men, yet an increase in leptin occurred upon their transition from an omnivorous to a meat-rich diet (p = 0.019). Examination of plasma adiponectin/leptin ratio, a proposed marker of cardiovascular risk, did not differ after 4-weeks of dietary intervention. Our study revealed that adiponectin and leptin concentrations are sensitive to short-term dietary intervention in a sex-dependent manner. This dietary modification of leptin and adiponectin not only occurs quickly as demonstrated in our study, but it remains such as published in studies with individuals who are established (long-term) vegetarians compared to omnivorous.
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Background: Dietary intake is a powerful modifiable factor that influences cancer risk; however, most US adults do not adhere to dietary guidelines for cancer prevention. One promising pathway for improving dietary adherence is targeting grocery shopping habits. Interventions might facilitate healthy grocery choices, with a combination of mHealth and traditional methods, by promoting the salience of dietary goals while shopping, enhancing motivation to make dietary changes, and increasing household support for healthy food purchasing. Objective: This pilot study will assess feasibility and acceptability of intervention components designed to improve adherence to dietary guidelines for cancer prevention (preliminary aim). The primary aim of the study is to quantify the effect of each intervention component, individually and in combination, on dietary intake (primary aim) and grocery store food purchases (exploratory aim). Mediation analyses will be conducted to understand the mechanisms of action (goal salience, motivation, and household support-secondary aims). The overarching goal is to optimize an mHealth intervention to be tested in a future fully powered clinical trial. Methods: The study enrolled adults (N=62) with low adherence to dietary recommendations for cancer prevention. In a 20-week program, all participants attend a nutrition education workshop and receive weekly educational messages through an app. A factorial design is used to test 4 intervention components: (1) location-triggered messages: educational messages are delivered when arriving at grocery stores; (2) reflections on the benefits of change: content is added to messages to encourage reflection on anticipated benefits of healthy eating, and participants attend an additional workshop session and 3 coach calls on this topic; (3) coach monitoring: food purchases are monitored digitally by a coach who sends personalized weekly app messages and conducts 3 coaching calls that focus on feedback about purchases; and (4) household support: another adult in the household receives messages designed to elicit support for healthy food purchasing, and support is addressed in 3 coach calls and an extra workshop session attended by the index participant and household member. Assessments are completed at weeks 0, 10, and 20 using self-report measures, as well as objective capture of grocery data from the point of purchase using store loyalty accounts. Results: The National Cancer Institute funded this study (R21CA252933) on July 7, 2020. Participant recruitment began in the spring of 2021 and concluded with the successful enrollment of 62 participants. Data collection is expected to be completed in the summer of 2022, and results are expected to be disseminated in the summer of 2023. Conclusions: The results of this study will inform the development of scalable interventions to lower cancer risk via changes in dietary intake. Trial registration: ClinicalTrials.gov NCT04947150; https://clinicaltrials.gov/ct2/show/NCT04947150. International registered report identifier (irrid): DERR1-10.2196/39669.
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Objective: To describe the pattern and prevalence of food and drink advertisements to children on commercial television in Sydney, Australia, and compare these with advertising regulations set out in the Children's Television Standards and results from a similar study in 2002. Design: Data were collected by recording television from 06.00 hours until 23.00 hours on all three commercial channels from Sunday 14 May 2006 to Saturday 20 May 2006 (357 h). The study analysed advertisements in two children's viewing periods, one as defined in the 2002 study and the other according to current standards. Food advertisements were coded using 18 food categories and were analysed by time period and popular children's programmes. Results: Food advertisements occurred in similar proportions during children's viewing hours and adult's viewing hours (25.5 vs. 26.9% of all advertisements, respectively), although there was a higher rate of high-fat/high-sugar food advertisements during children's viewing hours (49 vs. 39% of all food advertisements, P < 0.001). There were even more advertisements for high-fat/high-sugar foods during popular children's programmes, contributing to 65.9% of all food advertisements. Estimates of exposure indicate that children aged 5-12 years were exposed to 96 food advertisements, including 63 high-fat/high-sugar advertisements per week. Since 2002, there has been a reduction in overall food and high-fat/high-sugar food advertisements. Conclusion: Despite reductions in overall levels of food advertising, children continue to experience high levels of exposure to food advertisements, which remain skewed towards unhealthy foods. Further food advertising regulation should be required to curtail the current levels of advertising of high-fat/high-sugar foods to children, to make them commensurate with recommended levels of consumption.
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The protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss. To determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults. A randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998. Four university nutrition and obesity clinics and 2 contract clinical research clinics. Fifty-four lean (body mass index, 20.0-27.5 kg/m2; mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m2; mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years. Recombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0.03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight. Body weight, body fat, and incidence of adverse events. Weight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from -0.4 (2.0) kg for placebo (n = 36) to -1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from -0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to -7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks. Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects. A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.
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The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight1, 2. However, in the current ‘obesogenic’ human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions3. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans1, 4, 5. Here we show, using functional magnetic resonance imaging, that peptide YY3–36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.
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A summary of 50 years' work on the biology and behavior of honeybees. Liberally illustrated. Harvard Book List (edited) 1971 #215 (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Reducing food marketing to children has been proposed as one means for addressing the global crisis of childhood obesity, but significant social, legal, financial, and public perception barriers stand in the way. The scientific literature documents that food marketing to children is (a) massive; (b) expanding in number of venues (product placements, video games, the Internet, cell phones, etc.); (c) composed almost entirely of messages for nutrient-poor, calorie-dense foods; (d) having harmful effects; and (e) increasingly global and hence difficult to regulate by individual countries. The food industry, governmental bodies, and advocacy groups have proposed a variety of plans for altering the marketing landscape. This article reviews existing knowledge of the impact of marketing and addresses the value of various legal, legislative, regulatory, and industry-based approaches to change. *This PDF was amended on Aug. 5, 2009: See explanation at http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.pu.30.090805.200009
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To assess the biological activity and tolerability of pegylated recombinant native human leptin (PEG-OB), 30 obese men (mean body mass index, 33.9 kg/m2) were randomized to a double-blind treatment with weekly sc injections of 20 mg PEG-OB or placebo for 12 weeks, in addition to a hypocaloric diet (deficit, 2 MJ/day). Body composition, energy expenditure, and metabolic parameters were measured before and after treatment. PEG-OB was generally well tolerated based on adverse event reports, lab values, and vital signs. Weekly sc PEG-OB led to sustained serum concentrations of PEG-OB and leptin throughout treatment. No significant differences in the delta or percent weight loss, percent body fat, sleeping metabolic rate, or respiratory quotient were observed between the PEG-OB and placebo groups. Percent change in serum triglycerides from baseline was significantly correlated with body weight loss in the PEG-OB group, but not in the placebo group. Although larger reductions in serum triglycerides were observed in the PEG-OB group compared with the placebo group, these differences were not statistically significant. We concluded that weekly injection of PEG-OB leads to sustained serum concentration of PEG-OB and leptin throughout the 12-week treatment period and is generally well tolerated. The trends observed in serum triglycerides suggest that a weekly 20-mg sc treatment with PEG-OB may have biological effects in obese men.
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Evidence has existed for more than 50 years in support of the hypothesis that body energy stored in the form of fat is homeostatically regulated. Implicit in this concept is the existence of a biological system that operates dynamically over time to match cumulative energy intake to energy expenditure. For example, to compensate for weight loss induced by energy restriction, animals must enter a period of positive energy balance (i.e., energy intake greater than energy expenditure) that is sustained for as long as it takes to correct the deficit in body fat stores. Having reached this point, the animal must return to a state of neutral energy balance if stable fat mass is to be maintained. The identification of neuronal circuits in the hypothalamus that, when activated, exert potent, unidirectional effects on energy balance provides a cornerstone of support for this model. The additional finding that these central effector pathways are regulated by humoral signals generated in proportion to body fat stores, including the hormones insulin and leptin, helps to round out the picture of how energy homeostasis is achieved. The goal of this overview is to highlight the evidence that specific subsets of hypothalamic neurons containing specific signaling molecules participate in this dynamic regulatory process, and to put these observations in the larger context of a biological system that controls body adiposity.