Hepatic oleate synthesis restores SREBP‐1 processing and lipogenesis in SCD1‐deficient mice

Stearoyl‐CoA desaturase (SCD) catalyzes the de novo synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acid precursors. Previous work has demonstrated that SCD1 deficiency impairs hepatic lipogenesis and protects against development of diet‐induced obesity. The objective of this study was to determine if liver‐specific MUFA synthesis restores hepatic lipogenesis and processing of the sterol regulatory element binding protein‐1 (SREBP‐1) in SCD1 global knockout mice (GKO). We produced transgenic mice expressing human SCD5 only in liver and introduced this transgene into GKO mice. Hepatic SREBP‐1 maturation is increased in the hSCD5/GKO mice while increased expression of several important lipogenic genes also occurs. Unlike GKO mice fed a high carbohydrate, very low fat diet, hSCD5/GKO mice are largely protected from the dramatic weight loss that occurs. These results suggest that the product of the reaction catalyzed by hSCD5, 18:1n‐9, is involved in the regulation of SREBP‐1 processing as well as lipogenesis. Supported by NIH.