microRNA profiling unravels an abundant bta-miR-181a_R-1 that regulates yak adipogenic differentiation via the...

Yaks (Bos grunniens) have evolved distinctive metabolic adaptations that enable survival under the prolonged cold and nutrient-deficient conditions of the Qinghai-Tibetan Plateau. Adipose tissue plays a pivotal role in maintaining energy homeostasis. The proliferation and differentiation of preadipocytes are critical for the development of adipose tissue in bovines. MicroRNAs (miRNAs) are small regulatory molecules that participate in many cell biological processes, including development, differentiation, apoptosis, and metabolism. However, the expression profiles and functional roles of miRNAs in yak lipid metabolism remain largely unknown. To elucidate the molecular mechanisms underlying yak adipogenesis, we performed miRNA sequencing during yak preadipocyte differentiation and identified stage-specific expression profiles. Data analysis indicated that 252 (day 12 vs day 0), 167 (day 12 vs day 2), and 103 (day 2 vs day 0) miRNAs were differentially expressed in three stages, respectively. Further analysis identified 13 differentially co-expressed miRNAs across the three stages. Among the differentially co-expressed miRNAs, bta-miR-181a_R-1 was markedly upregulated during adipogenic differentiation. Functional assays revealed that bta-miR-181a_R-1 dramatically increased triglyceride accumulation and the expression of adipogenic marker genes (PPARγ, FABP4, and C/EBPα, P < 0.05), whereas it did not significantly affect preadipocyte proliferation. Mechanistically, bta-miR-181a_R-1 directly targeted sirtuin 1 (SIRT1), resulting in enhanced acetylation of forkhead box O1 (FoxO1) and promotion of lipid deposition via the FoxO signaling pathway. These findings reveal a novel miR-181a_R-1/SIRT1/FoxO1 regulatory axis that promotes yak adipocyte differentiation, providing new insights into miRNA-mediated adipogenesis in ruminants and a potential molecular basis for improving fat deposition in high-altitude livestock.