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Abstract
The ketogenic diet (KD) has been widely used in weight and glycemic control, although
potential side effects of long-term KD treatment have caused persistent concern. In
this study, we hypothesized that the KD would ameliorate the progression of diabetes
but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model
of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered
streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated
glucose and insulin tolerance in KD-fed diabetic mice was found, although the body
weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of
adipose tissue in KD mice was greater than in the other groups. The KD diet resulted
in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover,
the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed
significant changes in several key genes such as sterol regulatory element-binding
protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor
α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin
tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and
hepatic steatosis were observed, which should be considered carefully in the long-term
application of KD.