Backgrounds: It's well known that calorie restriction (CR) brings striking benefits in metabolic improvement with complex and unclear mechanism. In this study, we aimed to investigate the specific manifestation and possible mechanisms of metabolism in CR mice.

Methods: B6 mice were randomly assigned to three groups: (1) chow diet (control) , (2) chow diet with 40% calorie restriction (CR) , (3) high-fat diet (HFD) . The metabolism status and related examination were performed after 12 weeks of feeding.

Results: In this study, we found that CR increased fasting blood glucose and plasma insulin, as well as reduced insulin sensitivity reflected by insulin tolerance test. Comparing to the control mice, the decrease of phosphorylation levels of IRS-1 including serine307 and tyrosine632 residues, and AKT (threonine308) after insulin rejection further confirmed that CR induced insulin resistance. Different from insulin resistance induced by HFD, CR improved glucose tolerance and reduced gluconeogenesis. Meanwhile, CR led to absolute lipid reduction, manifested in decreased plasma lipid, liver lipid deposition and fat mass. In contrast, liver glycogen increased dramatically. Fasting glycogen was twice as much as that of HFD group and 20 times as that of control group. Furthermore, the CR increased p-PYGL, p-GSK3β and decreased p-GS notably indicating active glycogen synthesis and decomposition. Subsequently, we found that CR increased plasma corticosterone and decreased plasma c-reactive protein (CRP) compared with control and HFD groups, while plasma corticosterone and CRP in HFD were higher than those in control group. Additionally, CR lowered levels of orexigenic neuropeptides and elevated levels of anorexigenic neuropeptides.

Conclusions: Our study suggested that CR induced lipid insufficiency and stress from starvation, resulting in physiological insulin resistance and enhanced glycogen metabolism, including increased glycogen synthesis, glycogenolysis and glycogen content.


L.Hu: None. X.Xia: None. Y.Gu: None. J.Yin: None.


National Natural Science Foundation of China (No. 82070885) ,Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20172025)

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