BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

BACKGROUND:In recent years,the incidence of hyperuricemia caused by purine metabolism disorders has been increasing,which can induce inflammatory responses and lead to renal injury. OBJECTIVE:To explore the role and mechanism of solute carrier family 2 member 12(SLC2A12)in hyperuricemia-related renal injury. METHODS:Renal tubular cells(HK2 cells)were divided into five groups:HK2 group,HK2+uric acid group,HK2+uric acid+NC group,HK2+uric acid+siSLC2A12 group,and HK2+uric acid+siSLC2A12+MK-2206 group.HK2 cells were treated with uric acid and transfected with siRNA SLC2A12,followed by MK-2206 treatment to inhibit AKT expression.Cell proliferation was detected by CCK-8 assay.Apoptosis was detected by TUNEL assay.qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway.The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group.The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group.Compared with the HK2+uric acid+siSLC2A12 group,the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells.(2)Compared with the HK2 group,the connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA)and transforming growth factor beta(TGF-β)expressions increased in the HK2+uric acid group;CTGF,α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,the CTGF,α-SMA and TGF-β expressions decreased.(3)Compared with the HK2 group,the expression of p-AKT,FOXO3a,and p-FOXO3a elevated in the HK2+uric acid group;the expression of p-AKT further increased,while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,p-AKT expression decreased;FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group.(4)Compared with the HK2 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels increased in the HK2+uric acid group;interleukin-6,interleukin-1 β,and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group.(5)These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway.