Key result
Thermoneutral housing aggravated western diet-induced obesity, diabetes, and steatosis in male mice compared to standard housing, and revealed defective brown adipose tissue activation.
Why the study?
Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis, evaluate therapeutic approaches, and study the liver-adipose tissue dialog.
Thermoneutral housing exacerbates western diet-induced MASLD and impairs brown adipose tissue activation in mice, demonstrating its critical role in preclinical metabolic modeling.
Thermoneutral housing may improve translational validity of mouse metabolic studies; leaves open whether standard conditions confound BAT and steatosis research.
Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis and evaluate therapeutic approaches. The majority of the lipids accumulating in the liver upon MASLD originate from adipose tissue and appropriate models to study the liver-adipose tissue dialog are also needed. Here, we demonstrated that, compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis compared to standard-housed mice. We next used thermoneutral-housed WD-fed mice to question the effect of MASLD during β3-adrenergic stimulation. We found that diet-induced MASLD is associated with defective inter-organ metabolic cross-talk which leads to impaired activation of brown adipose tissue.
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Martin et al. (2025) studied Metabolic dysfunction-associated steatotic liver disease (MASLD). Thermoneutral housing vs. Standard temperature housing was evaluated on Obesity, diabetes, steatosis, hepatic inflammation, and fibrosis. Thermoneutral housing aggravated western diet-induced obesity, diabetes, and steatosis in male mice compared to standard housing, and revealed defective brown adipose tissue activation.
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