Institute of Clinical Physiology, National Research Council, Pisa, Italy.
Handb Exp Pharmacol. 2022;274:145-164. doi: 10.1007/164_2021_573.
Obesity is a key player in the onset and progression of insulin resistance (IR), a state by which insulin-sensitive cells fail to adequately respond to insulin action. IR is a reversible condition, but if untreated leads to type 2 diabetes alongside increasing cardiovascular risk. The link between obesity and IR has been widely investigated; however, some aspects are still not fully characterized.In this chapter, we introduce key aspects of the pathophysiology of IR and its intimate connection with obesity. Specifically, we focus on the role of adipose tissue dysfunction (quantity, quality, and distribution) as a driver of whole-body IR. Furthermore, we discuss the obesity-related lipidomic remodeling occurring in adipose tissue, liver, and skeletal muscle. Key mechanisms linking lipotoxicity to IR in different tissues and metabolic alterations (i.e., fatty liver and diabetes) and the effect of weight loss on IR are also reported while highlighting knowledge gaps.
肥胖是胰岛素抵抗（IR）发生和进展的关键因素，IR 是指胰岛素敏感细胞不能充分响应胰岛素作用的一种状态。IR 是一种可逆的状态，但如果不加以治疗，会导致 2 型糖尿病，同时增加心血管风险。肥胖与 IR 之间的联系已经得到了广泛的研究；然而，有些方面仍未得到充分描述。在这一章中，我们介绍了 IR 的病理生理学的关键方面及其与肥胖的密切关系。具体来说，我们专注于脂肪组织功能障碍（数量、质量和分布）作为全身 IR 的驱动因素的作用。此外，我们还讨论了在脂肪组织、肝脏和骨骼肌中发生的与肥胖相关的脂质组重塑。报告了将脂毒性与不同组织中的 IR 以及代谢改变（即脂肪肝和糖尿病）联系起来的关键机制，以及体重减轻对 IR 的影响，同时突出了知识空白。
