Expression of seipin in adipose tissue rescues lipodystrophy, hepatic steatosis and insulin resistance in seipin null mice

Biochemical and Biophysical Research Communications
Mingming GaoGeorge Liu

Abstract

Gene mutations in an ER protein seipin result in congenital generalized lipodystrophy (CGL) in humans, accompanied with hepatic steatosis and insulin resistance. Seipin gene is highly expressed in the brain, testis and adipose tissue. Seipin globally deficient mice (SKO) displayed similar phenotypes as human counterparts. It has been demonstrated that adipose-specific seipin knockout mice at elder age were indistinguishable from SKO mice. Due to the large mass of adipose tissue in the body, we hypothesized that seipin in adipose tissue might be responsible for the multiple metabolism-related abnormalities in SKO mice. Transgenic mice with adipose-specific expression of human seipin gene driven by aP2 promoter were generated and crossed with SKO mice to obtain adipose-specific seipin reconstitute (Seipin-RE) mice. In comparison with wild-type (WT) and SKO mice, the Seipin-RE mice exhibited normal plasma triglyceride and non-esterified fatty acids upon fasting, recovered adipose tissue mass, restored epididymal and subcutaneous fat pads morphology and partially recovered plasma leptin and adiponectin levels. Moreover, hepatic steatosis and insulin resistance was also absent in these mice. Our study demonstrates that expression of...Continue Reading

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Citations

Nov 21, 2018·American Journal of Physiology. Endocrinology and Metabolism·Huan WangWei Huang
Nov 8, 2018·International Journal of Cell Biology·Aquiles Sales Craveiro SarmentoJulliane Tamara Araújo de Melo Campos
Aug 11, 2017·Annual Review of Cell and Developmental Biology·Tobias C WaltherRobert V Farese

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