A low-carbohydrate diet induces hepatic insulin resistance and metabolic-associated fatty liver disease

We demonstrate that the ketogenic diet a low carbohydrate diet can induce fibrosis and NASH regardless of body weight loss compared to high-fat diet (HFD) fed mice. KD-fed mice develop severe hepatic injury, inflammation, and steatosis. In addition, KD increases IL-6-JNK signaling and aggravates diet induced-glucose intolerance and hepatic insulin resistance compared to HFD. Notably, pharmacological inhibition of IL-6 and JNK reverses KD-induced glucose intolerance and restores insulin sensitivity. Overall design: Using metabolic, biochemical and omics approaches, we identified the effects of a KD on NASH and investigated the mechanisms by which KD induces hepatic insulin resistance, steatosis, and fibrosis