Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
Eur J Clin Invest. 2018 Nov;48(11):e13017. doi: 10.1111/eci.13017. Epub 2018 Sep 26.
Insulin resistance not only occurs in obesity, but also in lipodystrophy. Although adipose tissue mass affects metabolic fluxes and participates in interorgan crosstalk, the role of energy metabolism within white adipose tissue for insulin resistance is less clear.
A Medline search identified in vivo studies in humans on energy and lipid metabolism in subcutaneous (SAT) and visceral adipose tissue (VAT). Studies in adipocyte cultures and transgenic animal models were included for the better understanding of the link between abnormal energy metabolism in adipose tissue and insulin resistance.
The current literature indicates that higher lipolysis and lower lipogenesis in VAT compared to SAT enhance portal delivery of lipid metabolites (glycerol and fatty acids) to the liver. Thus, the lower lipolysis and higher lipogenesis in SAT favour storage of excess lipids and allow for protection of insulin-sensitive tissues from lipotoxic effects. In insulin-resistant humans, enhanced lipolysis and impaired lipogenesis in adipose tissue lead to release of cytokines and lipid metabolites, ultimately promoting insulin resistance. Adipose tissue of insulin-resistant humans also displays lower expression of proteins involved in mitochondrial function. In turn, this leads to lower availability of mitochondria-derived energy sources for lipogenesis in adipose tissue.
Abnormal mitochondrial function in human white adipose tissue likely contributes to the secretion of lipid metabolites and lactate, which are linked to insulin resistance in peripheral tissues. However, the relevance of adipose tissue energy metabolism for the regulation of human insulin sensitivity remains to be further elucidated.
胰岛素抵抗不仅发生于肥胖，也发生于脂肪营养不良。尽管脂肪组织质量影响代谢通量并参与器官间的串扰，但白色脂肪组织内能量代谢对胰岛素抵抗的作用尚不明确。
对人类皮下（SAT）和内脏（VAT）脂肪组织能量和脂质代谢的体内研究进行了 Medline 检索。还纳入了脂肪细胞培养和转基因动物模型的研究，以更好地理解脂肪组织异常能量代谢与胰岛素抵抗之间的联系。
目前的文献表明，与 SAT 相比，VAT 中的脂肪分解增加和脂肪生成减少会增加脂质代谢物（甘油和脂肪酸）向肝脏的门静脉输送。因此，SAT 中的较低脂肪分解和较高脂肪生成有利于储存多余的脂质，并保护胰岛素敏感组织免受脂毒性影响。在胰岛素抵抗的人群中，脂肪组织中脂肪分解增加和脂肪生成受损会导致细胞因子和脂质代谢物的释放，最终导致胰岛素抵抗。胰岛素抵抗人群的脂肪组织还显示出与线粒体功能相关的蛋白质表达降低。反过来，这导致脂肪组织中用于脂肪生成的线粒体衍生能量源的可用性降低。
人类白色脂肪组织中异常的线粒体功能可能导致脂质代谢物和乳酸的分泌，这与外周组织的胰岛素抵抗有关。然而，脂肪组织能量代谢对调节人体胰岛素敏感性的相关性仍有待进一步阐明。
