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mice with germline deletion of Retsat show no differences in hepatic triglycerides, cholesterol, phospholipids, or non-esterified fatty acids (NEFAs) when analyzed on a mixed 129Sv/C57BL/6 background. When backcrossed to C57BL/6N, hepatic triglycerides are increased, irrespective of feeding normal chow or HFD, whereas the abundance of many polar unsaturated lipid species is decreased. Although showing increased body weight, the whole-body and liver-specific insulin sensitivity of RetSat-deficient mice is not impaired. In contrast to these results are findings from adult C57BL/6J mice with acute liver-specific RetSat depletion. When fed normal chow, liver-specific RetSat knockdown does not induce major abnormalities. But when fed on a HFD, these mice accumulate fewer triglycerides in liver and show lower levels of triglycerides and NEFAs in the circulation. Moreover, blood glucose and insulin levels are reduced, in conjunction with increased glucose tolerance but comparable insulin sensitivity. Mechanistically, this is associated with decreased mRNA, protein, and target gene expression of carbohydrate response element-binding protein (ChREBP) |
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