The evolution of steatosis and fibrosis in mice on a MASH-inducing diet and the effects of housing temperature.

Obesity induction in mice requires high-fat diet exposure. While hepatic steatosis develops, progression to inflammation and fibrosis, as in humans, requires prolonged exposure and additional dietary factors. Immunosuppression at room temperature may slow this progression. We evaluated thermoneutrality's effect on MASH development using a fibrosis-inducing MASH (GAN) diet. Mice were fed either MASH or chow diet and housed at room temperature or thermoneutrality. MASH diet groups were sacrificed monthly from 4 to 7 months. Serum markers of hepatic function were analyzed, and liver histology assessed steatosis, inflammation, ballooning (NAS score), and fibrosis via Picrosirius Red staining. MASH diet increased body weight, liver-to-body mass ratio, and hepatic fat, with no difference between housing conditions. Housing temperature had minimal effects on MASH. Serum markers and hepatic fibrosis were similar across groups. NAS score was lower at 4 months in thermoneutral MASH mice but not by 7 months. Thermoneutrality did not significantly impact MASH development. These findings, alongside existing literature, suggest thermoneutral housing does not consistently enhance MASH progression in GAN MASH-fed mice.