基于AMPK/SIRT1-FOXO1信号通路探讨哺乳期 营养过剩对小鼠肥胖的影响.

Objective To elucidate the protein post-translational modification levels of the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) 一 forkhead box protein 01 (FOXO1) signaling pathway in the process of lactation nutrient overload affecting obesity in mice, and to identify new targets and strategies for preventing obesity. Methods Newly-born male C57BL/6 mice were randomly assigned to the control group (CON, 8 pups/dam) and the small litter control group (SC, 5 pups/dam). After weaning for 3 weeks, they were fed with a standard diet for 6 weeks to adulthood. The CON and SC groups were further divided into two subgroups: CON and high-fat control group (HFC); SC and small litter HFC (SHFC) group. Mice in the CON and SC groups continued to consume a standard diet, while mice in the HFC and SHFC groups were induced to obesity with a high-fat diet for 7 weeks. Mice were sacrificed at different time points for sample collection. Enzyme assays were utilized to measure lipid levels. Expression levels of proteins were analyzed by Western blotting, and liver cell steatosis were examined using Hematoxylin -Eosin (HE) staining. Results Compared with CON or HFC, the body fat, body weight, and serum triglyceride levels of the SC or SHFC groups were significantly higher (P<0.05), and the high-density lipoprotein cholesterol levels were lower (P<0»05) at each stage. At 16 weeks, the hepatic cell steatosis in the SHFC group was significantly higher than that in the SC group. Compared with CON or HFC, the levels of SIRT1 and phosphorylated AMPK protein in the SC or SHFC groups were continuously decreased (P<0.05》and the acetylated FOXO1 protein was continuously increased (P<0,05). Conclusion Nutrient overload during lactation can continuously reduce the phosphorylation of AMPK protein and increase the acetylation of FOXO1 protein through the epigenetic mechanism of the AMPK/SIRT1 -FOX--01 signaling pathway, leading to lipid metabolism disorders, fat accumulation, and obesity. [ABSTRACT FROM AUTHOR]