Role of Hepatic Monounsaturated Fatty Acid Synthesis in Metabolic Regulation

Abstract

Stearoyl‐CoA desaturase (SCD) catalyzes the de novo synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids. Past work demonstrated SCD1 deficiency impairs hepatic lipogenesis and protects against diet‐induced obesity. Our objective was to determine if hepatic MUFA synthesis is sufficient to restore the impaired lipogenic program in SCD1 global knockout mice (GKO). To address this, we produced liver‐specific transgenic mice expressing either human SCD5, which preferentially synthesizes oleate (18:1n‐9), or mouse SCD3, which preferentially synthesizes palmitoleate (16:1n‐7), and introduced these transgenes into GKO mice. Hepatic oleate synthesis largely prevented very‐low‐fat diet‐induced weight loss and increased white adipose tissue weight to a greater extent than hepatic palmitoleate. In females, hepatic SREBP‐1 maturation and lipogenic gene expression increased in hSCD5/GKO while expression of these genes remained low in mSCD3/GKO mice. Hepatic oleate increased plasma glucose levels greater than hepatic palmitoleate. This work suggests that hepatic MUFA are involved in regulation of lipogenesis and gluconeogenesis with oleate being more potent than palmitoleate. Supported by NIH.