Geloneze Bruno, de Lima-Júnior José Carlos, Velloso Lício A
Laboratory of Investigation in Metabolism and Diabetes-LIMED, University of Campinas, UNICAMP, Campinas, 13084-970, Brazil.
Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas-UNICAMP, Campinas, Brazil.
Drugs. 2017 Apr;77(5):493-503. doi: 10.1007/s40265-017-0706-4.
The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain-adipocyte axis.
下丘脑核中控制食物摄入和能量平衡的神经回路的复杂性，解释了肥胖预防和治疗中涉及的一些限制因素。弓状核中存在的两个主要神经元群体控制热量摄入和能量消耗：一个群体共同表达促食欲的刺鼠相关肽（AgRP）和神经肽Y，另一个群体表达厌食性促食欲神经肽阿黑皮素原和可卡因及苯丙胺调节转录物（POMC/CART）。除了整合来自神经递质和激素的信号外，调节能量稳态的下丘脑系统还受营养物质的影响。例如，富含脂肪的饮食会引发下丘脑炎症（小胶质细胞的反应性激活和增殖，这种情况称为神经胶质增生）。这一过程会产生对厌食性激素瘦素和胰岛素的抵抗，导致肥胖的发生。胰高血糖素样肽-1（GLP-1）受体激动剂（GLP-1RAs）越来越多地用于治疗2型糖尿病。一种化合物（利拉鲁肽）最近被批准用于治疗肥胖症。尽管大多数研究表明，GLP-1RAs主要通过对食物摄入的抑制作用来促进体重减轻，但在啮齿动物和人类中，天然GLP-1和一些GLP-1RAs所具有的其他中枢效应，促使未来的临床试验去探索这一类药物所观察到的有益效果背后可能存在的其他机制。在本文中，我们综述了探索GLP-1RAs在脑-脂肪细胞轴中作用机制的最相关数据。
