Introduction and Objective: An increasing number of individuals with normal weight are attempting weight loss through caloric restriction. However, most weight loss attempts are followed by weight regain, leading to weight cycling. Whether weight cycling poses metabolic risks, especially in normal-weight individuals, remains debated. This study aims to evaluate the effects of weight cycling on glucose and lipid metabolism in normal-weight mice using an animal model.Methods: C57BL/6J mice underwent a weight-cycling protocol for 24 weeks, consisting of a 3-week period of 60% CR followed by 3 weeks of ad libitum (AL) feeding, with this 6-week cycle repeated four times. Subsequently, the mice were fed a HFD ad libitum to assess the potential metabolic risks associated with weight cycling. Throughout the study, body weight, food intake, and fasting blood glucose levels were monitored regularly. Glucose metabolism was evaluated periodically using GTT and ITT., Western blot, qPCR,ELISA and biochemical assays were employed to assess fasting insulin levels, hepatic insulin resistance, hepatic inflammation, and hepatic and circulating lipid content.Results: In C57BL/6J mice, weight cycling led to impaired glucose tolerance in normal-weight mice, which was associated with downregulation of mRNA expression for glucose transporters and metabolic enzymes involved in glucose oxidative utilization. However, this impairment in glucose tolerance could be slowly compensated for over time, accompanied by the disappearance of related molecular phenotypes. When the weight-cycling mice were subsequently fed a high-fat diet, glucose tolerance was again impaired, with a significant increase in hepatic triglyceride content and a higher weight of epididymal white adipose tissue.Conclusion: In summary, our study underscore the potential metabolic risks associated with weight cycling and the potential hazards of weight loss in normal-weight individuals.
J. Lin: None. M. Ren: None. L. Yan: None. W. Wang: None. X. Hong: None.
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