Best Practice & Research Clinical Endocrinology & Metabolism
4Regulation of energy homeostasis by peripheral signals
Section snippets
The energy equation and the obesity epidemic
Food intake is one of the commonest behaviors we undertake on a daily basis, and one with profound consequences because food intake also comprises one side of the energy equation. The energy equation holds that if body weight is to remain stable, food intake (i.e. energy intake) must equal energy expenditure (i.e. metabolism plus the effects of exercise) over long intervals. If the energy equation is not in balance, body weight will drift upwards or downwards over time.1 In point of fact, there
Meals
Food intake in mammals, including humans, occurs in distinct bouts or meals, and the number and size of meals over the course of a day comprises the meal pattern. Most humans are quite habitual in that they eat approximately the same number of meals, and at the same time of day, on a daily basis.15., 16. There is, however, a considerable variation among individuals, with some having three meals a day, others four, others with small snacks interspersed, and so on. It is generally accepted that
Body fat regulation
The other important information needed to regulate body weight pertains to the amount of fat stored in the body (see Figure 1 above). That is, it is well known that if an individual loses body weight (e.g. by dieting), there is a tendency to eat more food and restore body weight when conditions allow. Analogously, if an individual voluntarily overeats, or is forced to overeat, and gain weight, there is a tendency to reduce food intake and lose the gained weight when conditions allow. This is
Integration of satiety and adiposity signals
The information about total body fat derived from insulin and leptin must be integrated with satiety signals as well as with other signals related to myriad other factors, including learning, the social situation, stress and so on, for the control system to be maximally efficient. Although the nature of these interactions is not well understood, several generalizations or conclusions can be made. For one, the negative feedback circuits related to body fat and meal ingestion can easily be
Central signals related to energy homeostasis
As an oversimplification, the neural circuits in the brain that control energy homeostasis can be subdivided into those which receive relevant sensory information (afferent circuits), those which integrate the information and those which control motor, autonomic and endocrine responses (efferent circuits). The discussion above has focused upon some of the relevant afferent satiety and adiposity signals and how they influence food intake. Peptides such as insulin, leptin and CCK can be
Melanocortins
This is a rapidly expanding area of research and beyond the scope of this review. Because of this, only a few generalizations will be made. As discussed above, the arcuate nucleus of the hypothalamus comprises a hub, where many kinds of signals related to energy homeostasis converge. Adiposity signals from the circulation interact with specific insulin and leptin receptors in the arcuate nucleus. Satiety signals entering the hindbrain are relayed to the arcuate and other hypothalamic areas. The
Summary
Several types of signal are involved in the regulation of energy homeostasis by the brain. Because appetite and meal initiation are generally not under homeostatic control, body weight is regulated by how much food is eaten once a meal begins. Satiety signals generated as ingested food interacts with the stomach and intestine contribute to satiation. Adiposity signals are detected directly in the brain and work by changing the sensitivity of satiety signals such that when individuals lose
Acknowledgements
The preparation of this review was supported by several grants from the United States National Institutes of Health.
References (175)
Motivation concepts in behavioral neuroscience
Physiology and Behavior
(2004)Obesity wars: molecular progress confronts an expanding epidemic
Cell
(2004)- et al.
Set points for body weight and fat
Behavioral Biology
(1977) - et al.
Set points, settling points, and the control of body weight
Physiology and Behavior
(1977) - et al.
Food intake in the real world: implications for nutrition and aging
Clinical and Geriatric Medicine
(2002) - et al.
Biomarkers of satiation and satiety
American Journal of Clinical Nutrition
(2004) Fuel partitioning and food intake
American Journal of Clinical Nutrition
(1998)- et al.
The selfish brain: competition for energy resources
Neuroscience and Biobehavioral Reviews
(2004) - et al.
Cholecystokinin decreases food intake in man
American Journal of Clinical Nutrition
(1981) - et al.
Gastrin releasing peptide reduces meal size in rats
Peptides
(1982)
Receptor subtype mediation of feeding suppression by bombesin-like peptides
Pharmacology and Biochemistry of Behavior
Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake
Physiology and Behavior
Enterostatin suppresses food intake following injection into the third ventricle of rats
Brain Research
Effect of intravenous administration of apolipoprotein A-IV on patterns of feeding, drinking and ambulatory activity in rats
Brain Research
Anorexia following the intrahypothalamic administration of amylin
Brain Research
Reduction of food intake in rats by intraperitoneal injection of low doses of amylin
Physiology and Behavior
Metabolic effects of glucagon in the Wistar rat
American Journal of Clinical Nutrition
Vagal mediation of the cholecystokinin satiety effect in rats
Physiology and Behaviour
Role of the liver in the metabolic control of eating: what we know—and what we do not know
Neuroscience and Biobehavioral Reviews
Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin
Peptides
Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats
Peptides
Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin
Gastroenterology
The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis
Neuron
The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
Gastroenterology
Lithium chloride, cholecystokinin and meal patterns: evidence that cholecystokinin suppresses meal size in rats without causing malaise
Appetite
Adiposity signals and the control of energy homeostasis
Nutrition
Mechanisms regulating leptin production: implications for control of energy balance
American Journal of Clinical Nutrition
Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight
Brain Research
Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities
Frontiers in Neuroendocrinology
Leptin enters the brain by a saturable system independent of insulin
Peptides
Differential permeability of the blood–brain barrier to two pancreatic peptides: insulin and amylin
Peptides
The source of cerebral insulin
European Journal of Pharmacology
Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography
Neuroscience Letters
Therapeutic controversy: Obesity—a modern-day epidemic
Journal of Clinical Endocrinology and Metabolism
The obesity epidemic is a worldwide phenomenon
Nutrition Reviews
The epidemic of obesity
Journal of Clinical Endocrinology and Metabolism
Signals that regulate food intake and energy homeostasis
Science
Central nervous system control of food intake
Nature
Monitoring of stored and available fuel by the CNS: implications for obesity
Nature Reviews Neuroscience
Is the energy homeostasis system inherently biased toward weight gain?
Diabetes
Body weight set-points: determination and adjustment
Journal of Nutrition
Metabolic hormones and regulation of body weight
Psychology Review
Hunger, eating and ill health
American Psychologist
The control of eating behavior in free living humans
Regulation of energy intake and the body weight: the glucostatic and lipostatic hypothesis
Annals of the New York Academy of Sciences
Regulation of food intake and obesity
Science
An energy sensor for control of energy intake
Proceedings of the Nutrition Society
Metabolic and glucostatic control of feeding
Proceedings of the Nutrition Society
The timing of meals
Psychological Review
The psychobiology of meals
Psychonomic Bulletin and Review
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Circadian clock gene variants and their link with chronotype, chrononutrition, sleeping patterns and obesity in the European prospective investigation into cancer and nutrition (EPIC) study
2022, Clinical NutritionCitation Excerpt :The biological mechanisms underlying the potential link between clock gene variants and obesity could be through the connection between the central nervous system (CNS) and peripheral tissues in night and day circadian cycles. An imbalance between these phases affect peripheral tissues signalling pathways in the CNS, and may provoke appetite and satiety dysregulation, thereby leading to weight gain and obesity [53]. Also, the CNS is a controller of hormonal homeostasis; thus, another potential mechanism involved in the development of overweight and obesity throughout life could go through hormonal impairment [54].
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2012, NeuropharmacologyCitation Excerpt :The importance of the CCK satiety signal, which acts at the brainstem, was considered minor, since it invoked little or no weight loss (Woods and Seeley, 2000). Similarly, other satiety signals were considered to have low potency relative to those proposed to act at hypothalamus (Woods et al., 2004). Discussion of the integrative role of brain structures outside of the hypothalamus was largely absent in reviews as recent as 2004.