Recently, ketogenic diet has been found to be effective on improving obesity. Fibroblast growth factor 21 (FGF-21) is an endocrine factor mainly synthesized in the liver and shown to impact the metabolism of multiple tissues. Here, we investigated the effect of intermittent ketogenic diet on obesity and the sensitivity of FGF-21. Eight-week-old C57BL/6 mice were subjected to a chow diet (CD group), a high fat diet (HFD group), an intermittent chow diet (iCD group) or an intermittent ketogenic diet (iKD group) for 16 weeks. The intermittent diet intervention began with an HFD and was alternated with a chow diet or a ketogenic diet biweekly. Although the average energy intake of iKD group was highest in the four groups, the body weight, fasting blood glucose, the body fat mass and the weight of liver, epididymal adipose tissues (eWAT), subcutaneous adipose tissue (sWAT) and brown adipose tissue (BAT) of iKD group were ameliorated remarkably when compared to HFD group. The insulin sensitivity of iKD group was greatly improved as well. Both the histological results and the quantification of liver triglyceride showed that hepatic steatosis was significantly alleviated in iKD group. Western blotting showed that lipid metabolism in liver was greatly improved by iKD. What’s more, the cold exposure test showed that the iKD group had the best cold tolerance in the four groups. The mRNA expression of FGF-21 was greatly upregulated and hepatic inflammation was ameliorated in livers of iKD group. HE staining showed that the adipocytes in eWAT and sWAT were smaller in iKD group. The whitening of BAT was also improved in iKD group. Both mRNA and protein levels of UCP1 and PGC1α were remarkably upregulated by iKD in eWAT, sWAT and BAT. The mRNA levels of FGFR1 and KLB, which are related to FGF-21 sensitivity, were observed to be improved in eWAT and sWAT. Our data demonstrated that iKD ameliorates diet-induced obesity and fatty liver, and improved insulin sensitivity and cold tolerance with improved FGF-21 signaling.


W. Guo: None. W. Wang: None. W. Li: None.

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