title: Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.
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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Juliang
authors.initials: J
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Jueping
authors.initials: J
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lan
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yunqiu
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ren
authors.affiliation: Qingdao Zhuboshi Biological Technology Co, Ltd, Qingdao, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: bdu.ecnu@gmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Du
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000178:diet therapy*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy*; D055423:Diet, Ketogenic / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology*; D005346:Fibroblast Growth Factors / Q000235:genetics; D018149:Glucose Intolerance / Q000178:diet therapy; D005951:Glucose Tolerance Test; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics
chemical_list: D001786:Blood Glucose; D047493:PPAR alpha; D012333:RNA, Messenger; D051779:Sterol Regulatory Element Binding Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: Glycemic control; Hepatic steatosis; Ketogenic diet; Lipid accumulation; Type 2 diabetes