Transcriptome and lipid metabolome of the subcutaneous fat of Tibetan sheep: A comprehensive analysis of the reduction in fat deposition upon resveratrol and β-hydroxy-β-methyl butyric acid supplementation

Previous research studies confirmed that resveratrol (RES) and β-hydroxy-β-methyl butyric acid (HMB) regulated the glucolipid metabolism. However, the mechanism underlying of RES and HMB on subcutaneous fat remains unclear in ruminant. This study investigated the effects of dietary RES and HMB supplementation on immune, oxidative, and morphological changes in subcutaneous fat of Tibetan sheep using transcriptomics and metabolomics analysis. One hundred and twenty male Tibetan lambs of similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups of 30 lambs each: 1) H group (basal diet without RES or HMB); 2) H-RES group (1.5 g/day RES); 3) H-HMB group (1250 mg/day HMB); and 4) H-RES-HMB group (1.5 g/day RES and 1250 mg/day HMB). The study included a pre-test period of 10 days and a formal experimental period of 90 days. The results showed that, the supplementation of RES and HMB in combination reduced the backfat thickness and adipocyte diameter (P < 0.05). Notably, dietary RES and HMB significantly influenced the composition of fatty acid in subcutaneous fat, including increased monounsaturated fatty acid (MUFA), such as C16:1 N7, C18:1 N9, C20:1 N9, C22:1 N9, C24:1 N9, C24:1 N, and decreased saturated fatty acid (SFA), such as C8:0, C10:0, C11:0, C24:0. The H-RES-HMB group enriched in the lipid-related signaling pathways, including "linoleic acid", "arachidonic acid", "tyrosine" and "retinol". The transcriptome and metabolome indicated ten key genes including PLA2G5, PLA2G2D, PTGES, TBXAS1, ALOX5, MAOA, TYR, UGT1A4, RDH5, and DHRS9) and five metabolites including PC(33:4), LPC(22:0), LPC(15:0), LPC(16:1), PC(42:8) were identified as key biomarkers. In conclusion, dietary RES and HMB supplementation regulated the lipid metabolism by modulating gene transcription and metabolism in Tibetan sheep.