Abstract:[Background] Sedentary behavior, which is common among patients with type 2 diabetes, blocks the blood glucose control. However, its specific mechanism is not fully clarified. [Objective] To simulate sedentary behavior by limiting the activity of mice, to elucidate the mechanism for the aggravation of glucolipid metabolism disorder in type 2 diabetes mice by this behavior, and thus to lay a theoretical basis for relevant health education and intervention. [Methods] Male C57BL/6J mice were used in this study. Mice were randomized into the normal (CON) group, type 2 diabetes model (MOD) group and type 2 diabetes with activity restriction (SED) group. Model mice were used in the MOD group and SED group, and for the SED group, the time for the activity of mice was controlled to simulate the sedentary behavior for 8 weeks. The metabolic disorder of glucose and lipids in mice was determined by kits and morphological observation. The damage of ileum was observed based on hematoxylin and eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Quantitative reverse transcription PCR (RT-qPCR) was used to determine the changes of fecal microbes in mice, and TBA kit to measure the content of total bile acid in serum and liver of mice. The mRNA and protein expression of farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) in ileum and liver of mice were detected by qPCR and Western blotting, respectively. [Results] Compared with the CON group, the MOD group showed in increase in blood glucose and lipids, insulin resistance, oral glucose tolerance disorder, and obvious intestinal pathological changes. Restriction of mouse activity enhanced the disorder of glucose and lipid metabolism in diabetes mice (P<0.05). The diabetes mice displayed imbalance in intestinal flora, as manifested by the reduction in beneficial bacteria and increase in harmful bacteria at phylum and genus levels, which was exacerbated by the restriction of mouse activity. The total bile acid content in serum and liver was higher in the MOD group than that in the CON group, and higher in the SED group than in the MOD group (P<0.05). The expression of FXR and TGR5 in the MOD group was lower than that in the CON group (P<0.01), and the expression of these receptors was further inhibited by activity restriction. Spearman’s correlation analysis also showed that glucolipid metabolism was in significant correlation with intestinal flora and bile acid, a metabolite of intestinal flora. [Conclusion] Activity restriction aggravated the disorder of glucose and lipid metabolism in T2DM mice, which may be related to the imbalance of intestinal flora and bile acid metabolism, and the further down-regulation of bile acid receptor.
