Key result
Ucp1 knockout alleviates cardiac hypertrophy in mice via increased FGF21 at 24°C but not 30°C.
Why the study?
The molecular mechanisms underlying the endocrine role of brown adipose tissue in pathological cardiac remodeling remain unclear.
Does Ucp1 knockout reduce abdominal aorta coarctation-induced pathological cardiac hypertrophy in mice?
Does Ucp1 knockout reduce abdominal aorta coarctation-induced pathological cardiac hypertrophy in mice?
Ucp1 knockout alleviates pressure overload-induced cardiac hypertrophy in mice at 24 °C via increased BAT-derived FGF21 secretion, highlighting a temperature-dependent endocrine heart-BAT axis.
Answers are grounded in this paper and cite their sources.
Preclinical UCP1-FGF21 effects on hypertrophy require caution against clinical translation; leaves open temperature-dependent BAT axis in human pressure overload.
Adipocytes play an important role in the regulation of cardiovascular health and disease. However, the molecular mechanisms underlying the endocrine role of brown adipose tissue (BAT) in pathological cardiac remodeling remain unclear. Herein, we show that uncoupling protein 1 (UCP1)-knockout ( Ucp1 KO) mice exhibit reduced abdominal aorta coarctation-induced myocardial hypertrophy compared with wild-type mice in a 24 °C environment. However, this effect is eliminated in a thermoneutral (30 °C) environment. Mechanistically, Ucp1 KO significantly upregulates the expression of fibroblast growth factor 21 (FGF21) in BAT, resulting in increased circulating FGF21 levels. Interscapular BAT resection in Ucp1 KO mice decreases plasma FGF21 levels and reverses the alleviated pathological hypertrophic phenotype. Additionally, activation of the integrated stress response after Ucp1 KO significantly upregulates FGF21 expression in BAT. In conclusion, Ucp1 knockout alleviates heart failure in mice maintained at 24 °C, an effect that is likely associated with increased secretion of FGF21 from BAT.
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Cheng et al. (2026) studied Pathological cardiac hypertrophy. Ucp1 knockout vs. Wild-type mice was evaluated on Myocardial hypertrophy (heart weight, cardiomyocyte size, fibrosis, and cardiac function). Ucp1 knockout alleviates abdominal aorta coarctation-induced pathological cardiac hypertrophy in mice maintained at 24 °C via increased FGF21 secretion, but this effect is eliminated at 30 °C.
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