Hepatic Stearoyl‐CoA desaturase 1 Deficiency Promotes Liver Inflammation Under High Carbohydrate Low Fat Diet Feeding

Abstract

High carbohydrate diet causes liver steatosis and inflammation. To understand the role of stearoyl‐CoA desaturase 1 (SCD1) in liver steatosis, we generated liver‐specific SCD1 deficient mouse models (SCD1‐LKO). Previously we showed that SCD1‐LKO mice were protected from liver‐steatosis with long term high carbohydrate feeding. In this study we further analyzed the effects of a short term (10 days) feeding of high‐sucrose‐very‐low‐fat (HSVLF) diet on SCD1‐LKO mice. Surprisingly, the HSVLF feeding led to a dramatic increase in liver inflammation in SCD1‐LKO but not in Lox control mice. Histological analysis on liver sections revealed no sign of steatosis in LKO and Lox mice fed with HSVLF. The expression of macrophage specific genes Emr1 (F4/80) and CD68 in liver was significantly higher in HSVLF‐fed LKO than Lox mice. However, macrophage infiltration was not detected. We subsequently observed an increased liver ER stress response in HSVLF‐fed LKO mice, which was consistent with a dramatic elevation of the plasma ALT level. Furthermore, supplementation of the SCD1 product oleate rescued liver inflammation, ER stress response and liver injury in SCD1‐LKO mice, whereas supplementation of the SCD1 substrate–stearate to HSVLF did not reverse these effects. These data indicate that hepatic SCD1 is both necessary and sufficient to prevent the high carbohydrate low fat diet induced liver inflammation.