频繁饮食对人体糖脂代谢及生物节律表达的影响

BackgroundPrevalence of glycolipid metabolism disorders is rising annually. Dietary patterns are recognized as key modulators of their pathogenesis. Improper eating habits cause circadian disruptionwhich can be mediated by multiple genes. Clarifying the role of different dietary methods is crucial to preventing the occurrence of metabolic diseases. Howeverrelevant epidemiological data and data of population studies are scant. ObjectiveTo investigate the effects of dietary frequency on human glycolipid metabolism and circadian gene expressionsthereby providing insights into the relationship between dietary frequency and disease risk in healthy populations. MethodsHealthy volunteers aged 1829 years with regular sleep-wake cyclesregular dietaryand moderate snack intake were recruited between April and May 2022. Twenty eligible participants were randomized into two groupsa three-meal groupn=10and a six-meal groupn=10for a crossover intervention. Participants in the three-meal group consumed main meals at 7001200and 1800. Those in the six-meal group received three additional glucose challenges75 g anhydrous glucose dissolved in 300 mL of waterat 10001500and 2000. Each intervention lasted 24 hours. Blood samples were collected at eight timepoints 700800100012001300160020000200to analyze serum metabolic markersincluding total cholesterolTCtriglyceridesTGlow-density lipoprotein cholesterolLDL-Chigh-density lipoprotein cholesterolHDL-C glucoseinsulinand leptin. The mRNA expression levels of circadian genes were detectedClockBmal 1Per 2Cry 1Ppar Sirt 1. ResultsA significant interaction effect between group and time was observed on TG levelsFinteraction =2.277 Pinteraction =0.032. A significant main effect of group presented on LDL-C levelsFgroup=4.803Pgroup=0.030while time exhibited a significant main effect on TC levelsFtime=2.092Ptime=0.048. No significant differences in TCTGLDL-Cor HDL-C levels were observed between the two groups at any time points P>0.05. A significant interaction effect between group and time was identified for blood glucose levelsFinteraction =3.926Pinteraction =0.001. The group showed a significant main effect on insulin levelsFgroup=12.240Pgroup<0.001and time demonstrated significant main effects on blood glucoseinsulinand leptin levelsFtime=10.8402.399and 4.347respectivelyPtime<0.05. Participants in the six-meal group exhibited higher blood glucose levels at 1200 and 2000elevated insulin levels at 1000 and 1600and lower leptin levels at 1600 compared to the three-meal groupP<0.05. A significant interaction effect between group and time was observed for the mRNA expression of Cry 1Finteraction =30.250Pinteraction<0.001. Significant main effects of group were detected for the mRNA expressions of ClockBmal 1Per 2Cry 1Ppar and Sirt 1Pgroup<0.05while significant main effects of time were noted for the mRNA expressions of Bmal 1Per 2Cry 1and Sirt 1 Ptime<0.05. Participants in the six-meal group displayed significantly higher mRNA expressions of Clock at 800 and 1300Per 2 at 8001600and 0200and Cry 1 at 700800and 1000 compared to the three-meal groupP<0.05. Converselysignificantly lower expressions of Bmal 1 at 10001200and 1300and Cry 1 at 2000 and 0200 were observed in the six-meal groupP0.05. ConclusionFrequent six-meal consumption elevates insulin and glucose levelsdisrupts metabolic homeostasisand alters circadian clock gene expression in phase and amplitude. These changes induce glucose metabolism dysregulationleading to circadian rhythm disruption.