Department of Endocrinology (Diabetes and Metabolism)Rigshospitalet, Copenhagen, Denmark
Department of Endocrinology (Diabetes and Metabolism)Rigshospitalet, Copenhagen, Denmark.
Eur J Endocrinol. 2017 Feb;176(2):R67-R78. doi: 10.1530/EJE-16-0488.
Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver.
功能失调的脂肪组织与 2 型糖尿病（T2D）的发病风险增加有关。功能失调的脂肪组织的一个特征是皮下脂肪组织的扩张能力降低，导致脂肪在参与 T2D 发病机制的器官和/或组织中异位储存，从而导致脂肪毒性。脂质在骨骼肌中的积累与胰岛素抵抗有关，但大多数先前的研究并不能证明任何因果关系。大多数研究都认为，导致胰岛素抵抗的不是肌肉内的脂质本身，而是二酰基甘油、脂肪酸 CoA 和神经酰胺等脂质中间产物，而这些中间产物的定位、组成和周转率在胰岛素抵抗和 T2D 的发展中起着重要作用。脂肪组织比以前认为的更为活跃，因此未来的研究应该着眼于检查脂质组成、细胞定位和脂质周转率的动态变化对胰岛素抵抗发展的确切作用。此外，脂肪的异位储存对不同表型中易患 T2D 的各种器官有不同的影响；因此，了解脂肪生成是如何被调节的，代谢结果的干扰以及决定不同人群脂肪组织扩张能力的因素是必要的。本研究综述了目前关于脂肪组织扩张能力假说的文献，以及由于脂肪组织扩张能力有限而导致的异位脂质积累如何与肌肉和肝脏的胰岛素抵抗相关。
