Sex- and age-associated factors drive the pathophysiology of MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex- and age-associated mechanisms underlying the pathophysiology remain poorly understood. Here we show distinct responses to a HFD between males and females. Our study underscores the need for utilizing both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals. Hepatology Communications 2024 Overall design: Young (7 weeks) and aged (52 weeks), male and female mice were fed a high-fat diet (HFD) or low-fat diet (LFD). Liver metabolome (>600 molecules) and transcriptome profiles were analyzed