Effects of Intermittent Fasting on Blood Sugar and Serum Metabolomics of High-Fat Diet-Induced Obesity Mice

Background: Intermittent fasting (IF) has a broad spectrum of benefits for obesity and related metabolic disorders. However, serum metabolic signatures from IF remain relatively unexplored, and it remains uncertain whether different IF approaches exert similar effects on metabolism. This study was designed to examine the effects of three distinct IF approaches time-restricted feeding (TRF), alternate-day fasting (ADF), and intermittent fasting 5:2 (IF 5:2)-on the serum metabolomics of obesity mice.Methods: Male C57BL/6 mice were placed on either a normal-fat diet (NFD) or a high-fat diet (HFD) for 10 weeks. The HFDfed mice were subsequently subjected to dietary intervention using ADF, TRF, and IF 5:2 for another 10 weeks. Parameters such as body weight, serum lipid levels, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose tolerance were assessed in each group. Hepatic lipid accumulation and pathological changes were examined using Oil Red O staining and hematoxylin and eosin (H&E) staining. Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of inflammatory factors. The impact of IF on serum metabolites was investigated through non-targeted metabolomics based on UHPLC HRMS/MS.Results: ADF, TRF, and IF 5:2 led to a significant reduction in body weight (p < 0.01), HOMA-IR (p < 0.01), and serum lipids level (p < 0.05) while also improving glucose tolerance in obese mice. All three IF approaches reduced hepatic lipid accumulation and decreased inflammation levels in adipose tissues of obese mice. Serum metabolomics analysis revealed 209 differential metabolites affected by IF. Pathway enrichment analysis identified 8 relevant pathways involved in IF.Conclusions: ADF, TRF, and IF 5:2 diets could attenuate obesity, hyperglycemia, insulin resistance, and inflammation induced by HFD. Furthermore, IF improved the serum metabolic patterns in obese mice.