Decreased fatty acid transporter FATP4 is a potential contributor to impaired fat utilization in aging mice

Fat plays a key role in maintaining energy balance and supporting various physiological processes. HuAge-related disorders in fat utilization are increasingly prevalent, contributing to impaired energy balance, heightened metabolic disease risk, and increased cardiovascular dysfunction. The mechanism of age-induced disorders of fat utilization remains unclear. This study aims to explore the key factor affecting fat digestion and absorption during aging. Mice of different ages were used to analyze the changes of physiological and metabolic parameters with aging, including metabolic rate, energy expenditure, lean mass and apparent digestibility. Results showed that respiratory energy metabolism declined and fat apparent digestibility decreased significantly by more than 4% with aging. Fat is initially hydrolyzed in the intestine through combined actions of digestive enzymes and bile acids. Thus, the pancreatic lipase activity and total bile acids content were measured. The results revealed no significant changes in these factors. Furthermore, factors affecting fat absorption including intestinal structure and transporters expression were assessed. It was found that the crypt depth and villi height did not change significantly with age. Notably, intestinal proteomics analysis indicated that the expression of fatty acid transporter protein 4 (FATP4) was reduced by more than 50% in aged mice. In conclusion, this study demonstrated that age-related decline in FATP4 expression is linked to impaired intestinal fat absorption. This association may underlie the decreased fat apparent digestibility and impaired fat utilization during aging. These findings reveal the intrinsic mechanisms of age-induced dysregulation of fat utilization and providing a theoretical basis for enhancing fat utilization in older adults.