MECHANISMS IN ENDOCRINOLOGY: The gut–brain axis: regulating energy balance independent of food intake

Abstract

Obesity is a global pandemic with a large health and economic burden worldwide. Body weight is regulated by the ability of the central nervous system, and specially the hypothalamus, to orchestrate the function of peripheral organs that play a key role in metabolism. Gut hormones play a fundamental role in the regulation of energy balance, as they modulate not only feeding behavior but also energy expenditure and nutrient partitioning. This review examines the recent discoveries about hormones produced in the stomach and gut, which have been reported to regulate food intake and energy expenditure in preclinical models. Some of these hormones act on the hypothalamus to modulate thermogenesis and adiposity in a food intake–independent fashion. Finally, I discuss the association in humans of these gut hormones to eating, energy expenditure, and weight loss after bariatric surgery.

Hormonal Gut–Brain Signaling for the Treatment of Obesity

“…Several neuronal subsets in the PVN synthesize and secrete neuropeptides that have a net catabolic action, including the thyrotropin-releasing hormone, corticotrophin-releasing hormone and oxytocin. The ventromedial hypothalamus (VMH) controls non-shivering thermogenesis in brown adipose tissue (BAT) through modulating sympathetic nervous system outflow [ 38 ].…”

“…Circulating ghrelin levels, conventionally called the “hunger hormone”, increase in response to fasting and decrease after re-feeding. In humans and rodents with obesity, ghrelin levels are lower than lean controls [ 38 ]. Ghrelin exerts its biological effects on the energy balance through the growth hormone secretagogue receptor [ 86 ], which is expressed in AgRP neurons of the ARC [ 87 ].…”

Computational Investigation of the Impact of the Ghrelin Hormone Gene Variation (R51q) on the Hormone-receptor Binding Pattern

“…1,2 This peptide was initially identified as a powerful stimulator of growth hormone (GH) release from the anterior pituitary, 3 but it has now become obvious that it serves many functions throughout the organs. Ghrelin regulates food intake and satiety, gastrointestinal motility, 4,5 lipid storage control, and glucose metabolism. 6 Moreover, it has cardiovascular effects, protects against ischemia/reperfusion injury in the heart, has anti-inflammatory properties, and reduces antioxidant stress in a variety of diseases.…”

Taxa metabólica de repouso pós-operatória como preditor de sucesso cirúrgico após bypass gástrico em Y de Roux

“…A perda de peso é acompanhada de adaptações endócrinas que aumentam o apetite e reduzem a saciedade, de modo a resistir à perda e favorecendo a manutenção do peso a longo prazo. No entanto, existem alterações metabólicas relacionadas às variações de peso, à desnutrição e ao controle de peso corporal e obesidade 50 .…”

“…A obesidade eleva os níveis de endocanabinóides no hipotálamo, e estes efeitos não são apenas homeostáticos, mas causa hiperfagia e aumenta a preferência de alimentos altamente palatáveis. Apesar de não estar principalmente dependente de armazenamento de energia, o controle não-homeostático do consumo alimentar é influenciado pelo déficit ou excesso de energia 50 . O sistema endocanabinoide parece estar envolvido na regulação do equilíbrio energético ao favorecer o aumento do consumo alimentar e a redução do gasto energético na obesidade e após a privação alimentar através do sistema nervoso autonômo 50 .…”