脂肪细胞增殖、线粒体功能和脂肪氧化失败可导致异位脂肪储存、胰岛素抵抗和II型糖尿病。

L Heilbronn, S R Smith, E Ravussin
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引用次数: 424

摘要

背景:肥胖增加与胰岛素抵抗和II型糖尿病风险增加有关已被广泛接受。用于解释这种联系的主要范式是门户/内脏假说。这一假说提出,脂肪的增加,特别是在内脏储存库,通过胰岛素敏感组织中的Randle效应导致游离脂肪酸通量增加和胰岛素作用抑制。目的:在这篇综述中,将讨论这一范式的局限性,并提出另外两种可能解释肥胖与胰岛素抵抗/糖尿病之间已建立的联系的范式。(A)异位脂肪储存综合征。有三条证据支持这一观点。首先,不能形成足够的脂肪组织(也称为“脂肪营养不良”)会导致严重的胰岛素抵抗和糖尿病。这被认为是脂质异位储存到肝脏、骨骼肌和胰腺分泌胰岛素的β细胞的结果。其次,大多数肥胖患者还会将脂质分流到骨骼肌、肝脏,可能还有β细胞。几项研究表明,脂质渗入骨骼肌和肝脏的程度与胰岛素抵抗高度相关,证明了这一发现的重要性。第三,脂肪细胞大小的增加与胰岛素抵抗和糖尿病的发展高度相关。增加的脂肪细胞大小可能代表脂肪组织不能扩张,因此不能适应增加的能量流入。综上所述,这些观察结果支持“获得性脂肪营养不良”假说,即肥胖与胰岛素抵抗之间存在联系。因此,异位脂肪沉积是添加剂或协同作用的结果,包括增加饮食摄入量,减少脂肪氧化和脂肪生成受损。(B)内分泌模式。这个概念是与“异位脂肪储存综合征”假说同时发展起来的。脂肪组织分泌多种内分泌激素,如瘦素、白介素-6、血管紧张素II、脂联素和抵抗素。从这个角度来看,脂肪组织作为一个内分泌腺发挥着至关重要的作用,分泌许多对远处组织代谢有重要影响的因子。结论:异位脂肪和脂肪细胞作为内分泌器官的新范式可能为研究肥胖环境与糖尿病发生风险之间的关系提供新的框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus.

Background: It is widely accepted that increasing adiposity is associated with insulin resistance and increased risk of type II diabetes. The predominant paradigm used to explain this link is the portal/visceral hypothesis. This hypothesis proposes that increased adiposity, particularly in the visceral depots, leads to increased free-fatty acid flux and inhibition of insulin-action via Randle's effect in insulin-sensitive tissues.

Objectives: In this review, limitations of this paradigm will be discussed and two other paradigms that may explain established links between adiposity and insulin resistance/diabetes will be presented. (A) Ectopic fat storage syndrome. Three lines of evidence support this concept. Firstly, failure to develop adequate adipose tissue mass (also known as 'lipodystrophy') results in severe insulin resistance and diabetes. This is thought to be the result of ectopic storage of lipid into liver, skeletal muscle and the pancreatic insulin-secreting beta cell. Secondly, most obese patients also shunt lipid into the skeletal muscle, the liver and probably the beta cell. The importance of this finding is exemplified by several studies demonstrating that the degree of lipid infiltration into skeletal muscle and liver highly correlates with insulin resistance. Thirdly, increased fat cell size is highly associated with insulin resistance and the development of diabetes. Increased fat cell size may represent the failure of the adipose tissue mass to expand and therefore to accommodate an increased energy influx. Taken together, these observations support the 'acquired lipodystrophy' hypothesis as a link between adiposity and insulin resistance. Ectopic fat deposition is therefore the result of additive or synergistic effects including increased dietary intake, decreased fat oxidation and impaired adipogenesis. (B) Endocrine paradigm. This concept was developed in parallel with the 'ectopic fat storage syndrome' hypothesis. Adipose tissue secretes a variety of endocrine hormones such as leptin, interleukin-6, angiotensin II, adiponectin and resistin. From this viewpoint, adipose tissue plays a critical role as an endocrine gland, secreting numerous factors with potent effects on the metabolism of distant tissues.

Conclusions: The novel paradigms of ectopic fat and fat cell as an endocrine organ probably will constitute a new framework for the study of the links between our obesigenic environment and the risk of developing diabetes.

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