Abstract 1898 SCD1 deficiency promotes hepatic fibrosis and cirrhosis under a high carbohydrate low-fat diet.

Stearoyl-CoA desaturase-1 (SCD1) is a critical enzyme involved in lipid metabolism that catalyzes the synthesis of saturated fatty acids into monounsaturated fatty acids (MUFA), primarily oleate (C18:1) and palmitoleate (C16:1), that are required for membrane fluidity. Absence of SCD1 promotes lipid saturation which is implicated in lipotoxicity. Our previous studies showed that SCD1 deficiency protects against obesity and fatty liver but promotes inflammation and endoplasmic reticulum stress. To delineate the long-term consequences of SCD1 deficiency on hepatic Fibrosis, we employed liver specific SCD1 (LKO) mice fed a high carbohydrate low fat diet for 20 weeks. All animal studies were conducted in accordance with the Institutional Animal Care and Use Committee guidelines at The University of Wisconsin-Madison. Histological analysis revealed that LKO mice developed extensive fibrosis with necroinflammation compared with LOX control counterparts. Further analysis revealed an increase in markers related to: fibrosis, such as Cluster of Differentiation 14 (Cd14), Keratin 8, and Type II (Krt8); cirrhosis, such as latent transforming growth factor beta binding protein 1 (Tgfβ-1), Type 1 collagen (Col1a1), Type 3 collagen (Col3a1), and Smooth muscle alpha-2 actin (Acta2). Since LKO mice are protected against obesity and fatty liver, our findings suggest a novel link between monounsaturated fatty acid insufficiency and cellular pathways leading to fibrosis and cirrhosis in the absence of steatosis. Funding by NIH.