Improvement of Non‐Alcoholic Fatty Liver Disease in Mice by Intermittent Use of a Fasting‐Mimicking Diet

Scope Liver plays a central role in maintaining lipid homeostasis which is dysregulated in non‐alcoholic fatty liver disease (NAFLD) caused by overload of dietary fat, increase in lipid synthesis, and alteration of fatty acid oxidation in the liver. In this study, we aimed to investigate whether intermittent calorie restriction using a fasting‐mimicking diet (FMD) is able to slow down the progression of NAFLD in mice. Methods and Results This study analyzed the intervention activity of a FMD low in carbohydrate/protein but high in dietary fibers with a NAFLD mouse model induced by high‐fat high‐sucrose diet (HFHSD). Intermittent application of the FMD reduces HFHSD‐induced obesity and glucose intolerance. The FMD decreases the size of adipocytes and elevates expression of lipolysis genes and HSL protein in white adipose tissue. HFHSD‐induced lipid accumulation in the liver is reduced by the FMD, accompanied by a reduction of macrophage marker in the liver. RNA sequencing reveals that the expression of a number of genes involved in fatty acid oxidation is elevated by the FMD. Conclusion The findings indicate that intermittent application of the FMD can improve NAFLD, at least in part, through increased lipolysis in white adipose tissue and elevated fatty acid oxidation in the liver.