Brain Regulation of Appetite and Satiety

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Interest in the control of feeding has increased as a result of the obesity epidemic and rising incidence of metabolic diseases. The brain detects alterations in energy stores and triggers metabolic and behavioral responses designed to maintain energy balance. Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem, whereas reward and motivation aspects of eating behavior are controlled by neurons in limbic regions and the cerebral cortex. This article provides an integrated perspective on how metabolic signals emanating from the gastrointestinal tract, adipose tissue, and other peripheral organs target the brain to regulate feeding, energy expenditure, and hormones. The pathogenesis and treatment of obesity and abnormalities of glucose and lipid metabolism are discussed.

Section snippets

Gut-brain connection

The gastrointestinal tract not only acts as a conduit for food but is also crucial for the digestion and absorption of nutrients. Visual, olfactory, and gustatory stimuli stimulate exocrine and endocrine secretions and gut motility even before food enters the mouth. Meal ingestion stimulates mechanoreceptors, resulting in a coordinated sequence of distension and propulsion to accommodate the mass of food and ensure digestion and nutrient absorption. The brain receives signals from the

Leptin-brain interaction

As mentioned earlier, the discovery of leptin was a major milestone in elucidation of the communication between the brain and energy stores. Leptin is expressed by adipocytes, and the concentrations of leptin in adipose tissue and plasma parallel the mass of adipose tissue and triglyceride content. Leptin is increased in obesity and falls with weight loss.35, 36 These changes are partly mediated by insulin. Leptin is transported via a saturable process across the blood-brain barrier. Moreover,

Other peripheral factors controlling feeding and metabolism

Insulin is secreted in response to meals and increases the storage of glycogen, fat, and protein. In peripheral tissues, insulin autophosphorylates the insulin receptor, leading to activation of the insulin receptor substrate (IRS) phosphatidylinositol 3-kinase (PI3K) enzyme system. Studies by Porte and colleagues,51 preceding the discovery of leptin, revealed a blood-to-brain insulin transport and binding of insulin to several regions in the brain. Most significantly, injection of insulin into

Hedonic mechanisms regulating appetite and satiety

Because eating provides energy substrates for metabolism, it is logical that eating behavior is subject to homeostatic controls described in the preceding sections; however, appetite is also driven by factors beyond physiologic needs. Food provides powerful visual, smell, and taste signals which can override satiety and stimulate feeding. We tend to overeat sweet and salty foods and consume less foods that are bitter or sour. The taste and smell of food can profoundly alter behavior; palatable

Summary

Eating behavior is critical for the acquisition of energy substrates. As discussed in this review, the gut-brain axis controls appetite and satiety via neuronal and hormonal signals. The entry of nutrients in the small intestine stimulates the release of peptides which act as negative feedback signals to reduce meal size and terminate feeding. Hormones and cytokines secreted by peripheral organs exert long-term effects on energy balance by controlling feeding and energy expenditure. Neurons

References (81)

  • P. Kievit et al.

    Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells

    Cell Metab

    (2006)
  • E.E. Jobst et al.

    The electrophysiology of feeding circuits

    Trends Endocrinol Metab

    (2004)
  • S.C. Woods et al.

    The role of insulin as a satiety factor in the central nervous system

    Adv Metab Disord

    (1983)
  • K.D. Niswender et al.

    Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities

    Front Neuroendocrinol

    (2003)
  • A.C. Könner et al.

    Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production

    Cell Metab

    (2007)
  • G. Kunos

    Understanding metabolic homeostasis and imbalance: what is the role of the endocannabinoid system?

    Am J Med

    (2007)
  • T. Kadowaki et al.

    The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS

    FEBS Lett

    (2008)
  • N. Kubota et al.

    Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake

    Cell Metab

    (2007)
  • A. Coope et al.

    AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus

    FEBS Lett

    (2008)
  • M.D. Deboer et al.

    Cachexia: lessons from melanocortin antagonism

    Trends Endocrinol Metab

    (2006)
  • S. Fulton et al.

    Leptin regulation of the mesoaccumbens dopamine pathway

    Neuron

    (2006)
  • J.D. Hommel et al.

    Leptin receptor signaling in midbrain dopamine neurons regulates feeding

    Neuron

    (2006)
  • G.R. Hervey

    The effects of lesions in the hypothalamus in parabiotic rats

    J Physiol

    (1959)
  • J. Mayer

    Bulletin of the New England Medical Center, Volume XIV, April–June 1952: the glucostatic theory of regulation of food intake and the problem of obesity (a review)

    Nutr Rev

    (1991)
  • G.C. Kennedy

    The role of depot fat in the hypothalamic control of food intake in the rat

    Proc R Soc Lond B Biol Sci

    (1953)
  • A.M. Ingalls et al.

    Obese, a new mutation in the house mouse

    J Hered

    (1950)
  • K.P. Hummel et al.

    Diabetes, a new mutation in the mouse

    Science

    (1966)
  • D.L. Coleman

    Effects of parabiosis of obese with diabetes and normal mice

    Diabetologia

    (1973)
  • D.L. Coleman et al.

    Effects of parabiosis of normal with genetically diabetic mice

    Am J Physiol

    (1969)
  • Y. Zhang et al.

    Positional cloning of the mouse obese gene and its human homologue

    Nature

    (1994)
  • S.C. Chua et al.

    Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor

    Science

    (1996)
  • G.P. Smith et al.

    Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats

    Am J Physiol

    (1985)
  • D.S. Liebling et al.

    Intestinal satiety in rats

    J Comp Physiol Psychol

    (1975)
  • F.S. Kraly et al.

    Effect of cholecystokinin on meal size and intermeal interval in the sham-feeding rat

    J Comp Physiol Psychol

    (1978)
  • S. Bi et al.

    Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors

    Am J Physiol Regul Integr Comp Physiol

    (2007)
  • A.S. Kopin et al.

    The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight

    J Clin Invest

    (1999)
  • K.G. Murphy et al.

    Gut hormones and the regulation of energy homeostasis

    Nature

    (2006)
  • R.L. Batterham et al.

    Gut hormone PYY(3–36) physiologically inhibits food intake

    Nature

    (2002)
  • M. Tschöp et al.

    Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

    Nature

    (2004)
  • P. Wiedmer et al.

    Ghrelin, obesity and diabetes

    Nat Clin Pract Endocrinol Metab

    (2007)
  • Cited by (0)

    This work was supported by National Institutes of Health grants R01-DK062348 and PO1 DK049210.

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