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标题：Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr^/+P1195L/+ mice fed high-fat-diet
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作者：Eun Young Lee ; Kenichi Sakurai ; Xilin Zhang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep17565
出版社：Springer Nature
摘要：High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant ( Insr ^{P1195L/ +}) mice exposed to HFD ( Insr ^{P1195L/ +}/HFD mice) revealed increased glucose-6-phosphatase ( G6pc ) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in Insr ^{P1195L/ +}/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr ^{P1195L/ +}/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr ^{P1195L/ +}/HFD liver. Reduced Cyp7a1 expression in Insr ^{P1195L/ +}/HFD liver was rescued by WAT transplantation, and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr ^{P1195L/ +}/HFD liver.