Department of Pharmacology School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia Diabetes and Obesity Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
J Endocrinol. 2014 Jan 15;220(2):T61-79. doi: 10.1530/JOE-13-0397. Print 2014 Feb.
Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action.
脂肪酸（FAs）是所有细胞的必需元素，它们作为能量底物、细胞结构成分和信号分子发挥着重要作用。将多余的能量摄入以脂肪的形式储存在脂肪组织中是一种进化优势，旨在防止饥饿，但在当今世界的大部分地区，人类面临着食物的无限供应，脂肪的过度积累现在是人类健康的主要风险，尤其是 2 型糖尿病（T2D）的发展。自首次认识到脂肪堆积、胰岛素作用降低和 T2D 风险增加之间的关联以来，已经提出了几种机制将过多的 FA 可利用性与胰岛素作用降低联系起来，其中一些机制是相互竞争或矛盾的。在过量膳食 FA 导致肌肉胰岛素抵抗的背景下，本文总结了这些机制的证据，肌肉是胰岛素刺激血糖清除的主要组织。它还概述了模型和测量中可能存在的问题，这些问题可能会阻碍或有助于提高我们对 FA 与胰岛素作用之间联系的理解。
