TAILIEUCHUNG - Chapter 074. Biology of Obesity (Part 5)

A central pathway through which leptin acts to regulate appetite and body weight. Leptin signals through proopiomelanocortin (POMC) neurons in the hypothalamus to induce increased production of α-melanocyte-stimulating hormone (α-MSH), requiring the processing enzyme PC-1 (proenzyme convertase 1). α-MSH acts as an agonist on melanocortin-4 receptors to inhibit appetite, and the neuropeptide AgRp (Agouti-related peptide) acts as an antagonist of this receptor. Mutations that cause obesity in humans are indicated by the solid green arrows. In addition to these human obesity genes, studies in rodents reveal several other molecular candidates for hypothalamic mediators of human obesity or leanness. . | Chapter 074. Biology of Obesity Part 5 Figure 74-5 J signal Decreased appetile Suireti Foud AS Kupot DU fiMKjnvakt E. su Longs PL Jiwhwi JI Loioolu J Hirrisen r erf 17th Edlboni httpi vwv. OM-isrTi d cin -Cprn Copyright Th CoSè nfoi nc. All right A central pathway through which leptin acts to regulate appetite and body weight. Leptin signals through proopiomelanocortin POMC neurons in the hypothalamus to induce increased production of a-melanocyte-stimulating hormone a-MSH requiring the processing enzyme PC-1 proenzyme convertase 1 . a-MSH acts as an agonist on melanocortin-4 receptors to inhibit appetite and the neuropeptide AgRp Agouti-related peptide acts as an antagonist of this receptor. Mutations that cause obesity in humans are indicated by the solid green arrows. In addition to these human obesity genes studies in rodents reveal several other molecular candidates for hypothalamic mediators of human obesity or leanness. The tub gene encodes a hypothalamic peptide of unknown function mutation of this gene causes late-onset obesity. The fat gene encodes carboxypeptidase E a peptide-processing enzyme mutation of this gene is thought to cause obesity by disrupting production of one or more neuropeptides. AgRP is coexpressed with NPY in arcuate nucleus neurons. AgRP antagonizes a-MSH action at MC4 receptors and its overexpression induces obesity. In contrast a mouse deficient in the peptide MCH whose administration causes feeding is lean. A number of complex human syndromes with defined inheritance are associated with obesity Table 74-2 . Although specific genes are undefined at present their identification will likely enhance our understanding of more common forms of human obesity. In the Prader-Willi syndrome obesity coexists with short stature mental retardation hypogonadotropic hypogonadism hypotonia small hands and feet fish-shaped mouth and hyperphagia. Most patients have a chromosome 15 deletion and reduced expression of the signaling .

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