Neuroendocrine regulation of nutrient partitioning.
Leptin is a satiety factor which acts within the hypothalamus to decrease the levels of several neuropeptides stimulating food intake (among them, neuropeptide Y [NPY]), while increasing those that inhibit food intake. These effects of leptin bring about decreased body weight. In vivo, leptin potentiates basal and insulin-stimulated glucose utilization, presumably its oxidation, and decreases fat storage. Leptin increases sympathetic-mediated energy dissipation, and the expression of uncoupling proteins-1, -2, and -3. In peripheral tissues (muscles, adipose, others), leptin decreases triglyceride content by increasing fatty acid oxidation, decreasing the activity/expression of esterification and lipogenic enzymes, and favoring lipolysis. It decreases the lipogenic activity of insulin. Ultimately, leptin depletes fat stores and promotes leanness. NPY, taken as one example of what an orexigenic agent may produce, increases food intake and body weight. It favors fat storage in adipose tissue by stimulating lipogenic activity. It decreases glucose utilization by muscles, making more glucose carbon available for lipogenesis. Effects of NPY result from vagus nerve-mediated hyperinsulinemia and overactivity of the hypothalamo-pituitary-adrenal axis. Thus, NPY favors fat stores, and ultimately obesity. Glucocorticoids are necessary for NPY effects to occur, because central administration of the neuropeptide in adrenalectomized animals is ineffective. Glucocorticoids also have genuine effects when administered centrally to normal rats. They increase the hypothalamic content of NPY and decrease that of CRH. This double neuro-peptidic change stimulates food intake, insulin output, adipose tissue storage ability, decreases the expression of uncoupling proteins-1 and -3, and increases body weight. Body weight homeostasis appears to require a finely tuned regulation of both leptin and glucocorticoids, with their respective opposite effects.
Rohner-Jeanrenaud
F
F
Laboratoires de Recherches Métaboliques, Geneva University School of Medicine, Switzerland. Jeanrenaud_Francoise@Lilly.com
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*
D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y