Abstract
Background
Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.
Methods
Chow-fed mice and mice subjected to prolonged high-fat diet (HFD) consumption for 20 weeks, followed by 24 weeks of dietary interventions to either induce weight gain, weight loss, or weight cycling, were assessed for metabolic perturbations. Feeding efficiency, hepatic steatosis, circulating lipids, leptin levels, and glucose homeostasis were measured.
Results
Weight cycling led to hyperphagia and rapid weight regain, matching the weights of mice continuously on HFD. Despite weight loss, adipose tissue inflammation persisted with elevated pro-inflammatory markers and impaired glucose uptake. HFD- induced dysregulation in hypothalamic expression of orexigenic peptides and synaptic plasticity markers persisted even after weight normalization suggesting long-lasting neural alterations. Weight-cycled mice exhibited higher leptin levels, increased hepatic lipid storage, and dysregulated glucose metabolism compared to those with consistent diets, indicating worsened metabolic effects by Yoyo dieting.
Conclusion
In sum, our study highlights significant metabolic risks associated with weight cycling, particularly following prolonged obesity. Persistent adipose tissue inflammation, perturbed neural peptide and plasticity markers and impaired glucose tolerance emphasize the need for effective and sustainable weight loss strategies to mitigate the adverse outcomes of weight regain and improve long-term metabolic health.