Thermoneutral housing does not accelerate metabolic dysfunction-associated fatty liver disease in male or female C57Bl/6J mice fed a Western diet

Autor: Julia R.C. Nunes, Tyler K.T. Smith, Peyman Ghorbani, Conor O'Dwyer, Natasha A. Trzaskalski, Habiba Dergham, Ciara Pember, Marisa K. Kilgour, Erin E. Mulvihill, Morgan D. Fullerton
Rok vydání: 2023
Předmět:
Zdroj: American Journal of Physiology-Endocrinology and Metabolism.
ISSN: 1522-1555
0193-1849
Popis: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a growing cause of mortality and morbidity and encompasses a spectrum of liver pathologies. While dozens of preclinical models have been developed to recapitulate stages of MAFLD, few achieve fibrosis using an experimental design that mimics human pathogenesis. We sought to clarify whether the combination of thermoneutral (TN) housing and consumption of a classical Western diet (WD) would accelerate the onset and progression of MAFLD. Male and female C57Bl/6J mice were fed a nutrient-matched low-fat control or Western diet (WD) for 16 weeks. Mice were housed with littermates at either standard temperature (TS; 22°C) or thermoneutral-like conditions (TN; ~29°C). Male but not female mice housed at TN and fed a WD were significantly heavier than TS -housed control animals. WD-fed mice housed under TN conditions had lower levels of circulating glucose compared to TS mice; however, there were select but minimal differences in other circulating markers. While WD-fed TN males had higher liver enzyme and higher liver triglyceride levels, no differences in markers of liver injury or hepatic lipid accumulation were observed in females. Housing temperature had little effect on histopathological scoring of MAFLD progression in males; however, while female mice retained a level of protection, WD-TN conditions trended toward a worsened hepatic phenotype, which was associated with higher macrophage transcript expression and content. Our results indicate that interventions coupling TN housing and WD-induced MAFLD should be longer than 16 weeks to accelerate hepatic steatosis and increase inflammation in both sexes of mice.
Databáze: OpenAIRE
Externí odkaz: