Integrated Transcriptomic and Metabolomic Analyses Reveal the Whitening of Perirenal Brown Adipose Tissue in Yak Calves

Brown adipose tissue (BAT) is essential for neonatal thermogenesis; however, in yak, the adipose tissue exhibits age-related changes from a brown-like to a white-like phenotype between postnatal day 1 (P1) and day 30 (P30). This exploratory study aimed to characterize the molecular and metabolic changes underlying this postnatal transition, with a particular focus on thermogenesis and lipid metabolism. Perirenal adipose tissue from yak calves at P1 and P30 was analyzed using phenotypic, transcriptomic (n = 3 per group), and metabolomic (n = 6 per group) approaches. Our results showed that multilocular adipocytes were abundant at P1, whereas unilocular adipocytes were predominant by P30, accompanied by significantly increased triglyceride content (p < 0.05). Transcriptomic and metabolomic analyses identified a total of 1000 differentially expressed genes (DEGs) and 17 differential metabolites between the two stages. From the DEGs, 13 thermogenesis-related genes and 24 lipid metabolism-related genes were selected based on functional relevance, and all 17 differential metabolites were analyzed. Integrative analysis of the transcriptomic and metabolomic datasets further identified 14 key genes related to thermogenesis and lipid metabolism and 6 differential metabolites potentially associated with these metabolic pathways. Among them, CDS2, GPAM, AGPAT2, CPT1C, GADD45B, PLIN1, and metabolites phosphatidylethanolamine (PE), phosphatidic acid (PA), and oxidized phosphatidylserine (PS) may serve as a potential link between lipid deposition and thermogenic metabolism. Fatty acid profiling showed that n-3 polyunsaturated fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) were enriched in BAT, while stearic acid (SA, 18:0) and oleic acid (OA, 18:1 n-9) were enriched in WAT. These findings suggest age-related changes in the molecular and metabolic characteristics of postnatal BAT from a thermogenic phenotype toward a lipid-storage state, consistent with a functional transition during adipose tissue development. This provides a molecular framework for understanding BAT phenotypic changes in neonatal yaks and identifies candidate targets for future studies investigating the regulation of thermogenesis and lipid metabolism in plateau ruminants.