American Diabetes Association
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Intermittent fasting improves glucose homeostasis not entirely dependent on caloric restriction in db/db male mice

posted on 2024-03-19, 19:11 authored by Dinghao Zheng, Xiaosi Hong, Xiaodan He, Jianghong Lin, Shujin Fan, Jinli Wu, Zhuoxian Liang, Sifan Chen, Li Yan, Meng Ren, Wei Wang


Intermittent fasting (IF), which involves prolonged fasting intervals accompanied by caloric restriction, is an effective dietary treatment for obesity and diabetes. Although IF offers many benefits, it is difficult to determine whether these benefits are the consequences of caloric restriction. Every-other-day feeding (EODF) is a commonly used IF research model. This study was designed to identify other effectors of EODF, in addition to caloric restriction, and the possible underlying mechanisms. Diabetic db/db mice were divided into three groups: ad libitum (AL), meal-feeding (MF) and EODF. The MF model was employed to attain a level of caloric restriction comparable to EODF, with food distribution evenly divided between 10 AM and 6 PM, thereby minimizing the fasting interval. EODF yielded greater improvements in glucose homeostasis than MF in db/db mice by reducing fasting glucose levels and enhancing glucose tolerance. However, these effects on glucose metabolism were less pronounced in lean mice. Furthermore, ubiquitination of the liver-specific glucocorticoid receptor (GR) facilitated its degradation, and downregulating Kruppel-like factor 9 (KLF9), which ultimately suppressed liver gluconeogenesis in diabetic EODF mice. Although GR and KLF9 might mediate the metabolic benefits of EODF, the potential benefits of EODF might be limited by elevated serum glucocorticoid (GC) levels in diabetic EODF mice. Overall, this study suggests that the metabolic benefits of EODF in improving glucose homeostasis are independent of caloric restriction, possibly due to the downstream effects of liver-specific GR degradation.


Clinical Research Center for Metabolic Diseases x 2020B1111170009 202102100004

Guangdong Basic and Applied Basic Research Foundation x 2019A1515011199 2021B1515020005 2023A1515030079

Guangdong Provincial Department of Science and Technology 2020B1212030004 2020B1212060018

Guangzhou Science, Technology and Innovation Commission > Guangzhou Municipal Science and Technology Program key projects 202206010031

Ministry of Science and Technology of the People's Republic of China > National Natural Science Foundation of China U20A20352


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