Effects of high-fat diet and age on locomotor activity and lipid metabolism in mice.

To investigate the effects of a high-fat diet (HFD) and age on energy metabolism and behavioral activity in small rodents, we measured body weight, food intake, body fat, metabolic rate, digestibility, blood lipid profile, insulin levels, small intestinal morphology, and behavioral activity in 3-, 6-, and 12-month-old male C57BL/6 J mice fed either a low-fat diet (LFD) or an HFD for 5 weeks. Mice fed an HFD exhibited lower energy intake, mucosal thickness, and muscularis thickness compared with those given the LFD and displayed increased fat accumulation accompanied by elevated insulin, blood glucose, and cholesterol levels. These changes were associated with increased digestibility and reduced energy expenditure. Furthermore, compared with the 3- and 6-month-old groups, the 12-month-old group exhibited higher energy intake and lower locomotor activity, which contributed to increased fat accumulation and body weight gain. Thus, fat accumulation induced by HFD and age is not solely due to excessive energy intake but also results from enhanced absorption efficiency and decreased energy expenditure. The combined effect of HFD and aging promoted the observed metabolic disorders and obesity. Moreover, distinct energy utilization strategies and behavioral patterns were observed across age groups, with age-specific differences in tissue responsiveness to HFD. Age-related metabolic abnormalities became apparent by 12 months of age, and HFD further accelerated their onset. In conclusion, HFD significantly amplifies the adverse effects of aging, and their combined action can promote the development of metabolic disorders and obesity. This study provides insight into the stage-specific effects of HFD in small rodents and advances understanding of aging-related metabolic dysfunction.