Gugliucci Alejandro
Glycation, Oxidation and Disease Laboratory, Department of Research, Touro University California-COM, Vallejo, CA, United States.
Adv Clin Chem. 2022;109:1-30. doi: 10.1016/bs.acc.2022.03.001. Epub 2022 Jul 13.
Dysfunctional visceral fat plays a key role in the initiation and maintenance of chronic inflammation, liver steatosis and subsequent systemic insulin resistance that primes the body for development of metabolic syndrome. These changes, occurring with or without obesity, lead to type 2 diabetes. In this chapter, we first provide a brief overview of the factors that lead to dysfunctional visceral fat and their relative importance. Adipose tissue has a great plasticity which allows for cell hypertrophy and, when needed, angiogenesis to sustain hypertrophy. Due to the prevalence of inexpensive and widely available "junk food," i.e., those enriched in fat, carbohydrate and sugar, this response becomes maladaptive. Hypertrophied adipocytes become hypoxic. Some undergo necrosis which induces macrophage recruitment forming crown structures wherein macrophages and leukocytes surround injured adipocytes. This leads to the ominous triad: inflammation, fibrosis (extracellular matrix hypertrophy) and impaired angiogenesis as well as consequent unresolved hypoxia. Adipokines and cytokines secreted by these crown structures as well as the palmitate fluxes due to excessive lipolysis are released from visceral adipose tissue to portal blood. They inundate the liver causing insulin resistance. In this review we explore the actions of adipokines, proteins and macrophage cytokines (adiponectin, leptin, FABP4, resistin, PAI-1, ANGPT3/4, IL-6 and TNFα) that normally intervene but whose action goes awry in the presence of inflammation and insulin resistance. We provide an assessment of their relative clinical utility as well as challenges associated with their use as biomarkers.
功能失调的内脏脂肪在慢性炎症、肝脏脂肪变性及随后的全身胰岛素抵抗的发生和维持中起关键作用，而全身胰岛素抵抗会促使机体发展为代谢综合征。这些变化无论是否伴有肥胖都会发生，进而导致2型糖尿病。在本章中，我们首先简要概述导致内脏脂肪功能失调的因素及其相对重要性。脂肪组织具有很大的可塑性，能够实现细胞肥大，并在需要时进行血管生成以维持肥大状态。由于价格低廉且广泛可得的“垃圾食品”（即富含脂肪、碳水化合物和糖的食品）的盛行，这种反应变得适应不良。肥大的脂肪细胞会出现缺氧。一些脂肪细胞会发生坏死，从而诱导巨噬细胞募集，形成冠状结构，其中巨噬细胞和白细胞围绕着受损的脂肪细胞。这会导致一个不祥的三联征：炎症、纤维化（细胞外基质肥大）和血管生成受损以及随之而来的持续性缺氧。这些冠状结构分泌的脂肪因子和细胞因子以及由于过度脂解产生的棕榈酸通量从内脏脂肪组织释放到门静脉血中。它们涌入肝脏，导致胰岛素抵抗。在本综述中，我们探讨了脂肪因子、蛋白质和巨噬细胞细胞因子（脂联素、瘦素、脂肪酸结合蛋白4、抵抗素、纤溶酶原激活物抑制剂1、血管生成素3/4、白细胞介素6和肿瘤坏死因子α）的作用，这些因子通常发挥干预作用，但在存在炎症和胰岛素抵抗的情况下其作用会出现偏差。我们评估了它们相对的临床效用以及用作生物标志物所面临的挑战。
