Hepatic Stearoyl‐CoA desaturase 1 safeguards liver from inflammation induced by a high carbohydrate low‐fat diet

Abstract

High carbohydrate feeding causes liver steatosis and inflammation. Using liver‐specific SCD1 knock‐out mice (SCD1‐LKO) fed with a high‐sucrose‐very‐low‐fat (HSVLF) diet for 10 days, we identified dramatic liver inflammation, liver injury, ER stress and activation of liver macrophages in these mice with no sign of steatosis. Given the minimal fat content in HSVLF, adipose tissue with intact SCD1 in LKO mice was, however, inert in mobilizing fatty acids. Conversely, supplementation of oleate (18:1), but not stearate (18:0), to HSVLF prevented the inflammation and ER stress in the liver, suggesting a distinct role of hepatic SCD1 in maintaining liver function when the diet is deficient of unsaturated fatty acids. Furthermore, analysis on mitochondria ROS production and membrane potential revealed no damage of liver mitochondria in SCD1‐LKO mice. However, electro‐microscopy analysis detected reduced ribosome in ER in the liver of SCD1‐LKO mice, indicating decreased protein production. As a result, we then identified that the plasma albumin was significantly lower in these mice, which likely led to the inability of adipose to mobilize fatty acids. Moreover, SCD1‐LKO mice fed with HSVLF for 10 weeks still exhibited liver inflammation. These data indicate that hepatic SCD1 is both necessary and sufficient in preventing liver inflammation induced by high carbohydrate low fat diet.