Lopes Heno F, Corrêa-Giannella Maria Lúcia, Consolim-Colombo Fernanda M, Egan Brent M
Universidade Nove de Julho-UNINOVE, Rua Vergueiro 235/249, 2 subsolo, Liberdade, São Paulo, CEP: 01504-001 Brazil ; Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Laboratório de Investigação Médica (LIM-18) e Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP Brazil.
Diabetol Metab Syndr. 2016 Jul 19;8:40. doi: 10.1186/s13098-016-0156-2. eCollection 2016.
The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of adipose tissue blocks lipolysis to a variety of lipolytic stimuli and adipose tissue send inputs to the brain. An imbalance of sympathetic/parasympathetic and alpha2 adrenergic/beta3 receptor is related to visceral adipose tissue storage and insulin sensitivity. Thus, in addition to the well-known factors classically associated with VAS, abnormal autonomic activity also emerges as an important factor regulating white adipose tissue, which highlights complex role of adipose tissue in the VAS.
在过去30年里,人体测量学指标(腰围)和血液动力学指标(血压)的变化与糖脂代谢异常之间的关联引发了诸多讨论。如今,血压、体重指数/腹围、血糖、甘油三酯血症以及高密度脂蛋白胆固醇浓度均被纳入代谢综合征的定义范畴,在本综述中被称为内脏型肥胖综合征(VAS)。然而,250多年前就已认识到内脏和纵隔肥胖与高血压、痛风及阻塞性呼吸暂停之间的关联。由于长期热量摄入过多导致内脏脂肪组织扩张,会促使巨噬细胞募集,这些巨噬细胞呈现出炎症表型并产生直接干扰胰岛素信号传导的细胞因子,进而导致胰岛素抵抗。反过来,胰岛素抵抗(IR)在多种组织中表现出来,促成了VAS的整体表型。例如,在白色脂肪组织中,IR会导致脂肪分解、游离脂肪酸释放增加以及炎症加剧,因为脂肪酸可与Toll样受体结合。在肝脏中,IR会导致肝葡萄糖生成增加,促成高血糖;在血管内皮和肾脏中,IR会导致血管收缩、钠潴留,进而引发动脉高血压。在VAS的发展过程中还发现了其他因素,如遗传易感性、与暴露于不利子宫内环境相关的表观遗传因素以及肠道微生物群。最近,实验和临床研究表明自主神经系统参与调节内脏脂肪组织。交感神经系统通过β1、β2、β3、α1和α2肾上腺素能受体与脂肪组织功能及分化相关。这种关系是双向的:脂肪组织的交感神经去支配会阻断对多种脂解刺激的脂肪分解作用,并且脂肪组织会向大脑发送信号。交感/副交感神经以及α2肾上腺素能/β3受体的失衡与内脏脂肪组织储存及胰岛素敏感性相关。因此,除了与VAS经典相关的众所周知的因素外,异常的自主神经活动也成为调节白色脂肪组织的一个重要因素,这凸显了脂肪组织在VAS中的复杂作用。