Cold-Induced DHRS4 Promotes Thermogenesis via Enhanced Fatty Acid β-Oxidation in Porcine Subcutaneous Adipocytes

Adipose tissue exhibits remarkable plasticity in adapting to thermal stress, yet the epigenetic mechanisms coordinating metabolic reprogramming in large mammals-particularly in livestock species lacking classical brown adipose tissue (BAT) such as swine-remain elusive. Using a porcine cold exposure model, we investigated adipose adaptation mechanisms through integrated single-cell RNA sequencing and bulk transcriptomic analyses of subcutaneous adipose tissue (subWAT). We identified a cold-induced thermogenic adipocyte subpopulation, characterized by upregulated DHRS4 expression. Mechanistically, cold exposure induced hypomethylation at the DHRS4 promoter locus, enhancing its expression to potentiate fatty acid β-oxidation, accompanied by thermogenic capacity upregulation. Our findings establish DHRS4 as an epigenetic-metabolic switch governing cold adaptation and a potential target for improving cold resistance in swine production systems.