Weight regain, but not weight loss exacerbates hepatic fibrosis during multiple weight cycling events in male mice.

ABSTRACT

PURPOSE: Weight cycling is a phenomenon characterized by fluctuating body weight that is commonly observed in individuals employing intentional weight loss methods. Despite its prevalence, the impact of weight cycling on health remains equivocal. The current investigation aimed to examine the effects of weight cycling on liver health. METHODS: The weight cycling model was established by switching the feeding method of mice between ad libitum (AL) and restricted intake (DR or 60% of AL) of the breeding diet to cause weight gain and weight loss, respectively. The weight cycling model comprised two and a half cycles, with one group terminating the experience during the weight-gain period (S-AL) and the other during the weight-loss period (S-DR). Liver tissue was collected to investigate morphology alterations, apoptosis, lipid metabolism, and mitochondrial homeostasis. RESULTS: The results demonstrated that the termination point of weight cycling affected body weight and hepatic steatosis. All parameters examined in the S-DR mice exhibited a comparable trend to those observed in the DR mice. Notably, S-AL mice showed a significant increase in lipid metabolism-related proteins in the liver compared to AL-fed mice, along with reduced lipid droplets. Moreover, hepatic apoptosis and fibrosis were exacerbated in the S-AL mice compared to AL mice, whereas mitochondrial fusion, biogenesis, and mitophagy were decreased in the S-AL mice. CONCLUSION: Weight cycling ending in weight gain exacerbated hepatic fibrosis, potentially by inducing apoptosis or disrupting mitochondrial homeostasis. Conversely, weight cycling ending in weight loss demonstrated beneficial effects on hepatic health.