Establishment of a subcutaneous adipogenesis model and distinct roles of LKB1 regulation on adipocyte lipid accumulation in high-altitude Bos grunniens

Abstract

ABSTRACT The domestic yak was regarded as a valuable model to explore the molecular mechanism of high-altitude animal adaptation, including the extreme tolerance of starvation and cold stress, which is closely associated with specifically seasonal deposition and metabolism of subcutaneous adipose tissue. However, the key regulators for these processes remain largely unknown. Here, the yak adipogenesis model in vitro was established and liver kinase b1 (LKB1) was regarded as a key negative regulator involved in yak adipocytes lipid accumulation. First, the mRNA level of LKB1 in adipose tissue of yaks from the cold season is significantly higher than that of yaks from the warm season. Interestingly, overexpression of LKB1 significantly inhibited adipocytes lipid accumulation. Consistently, LKB1 overexpression dramatically suppressed mRNA levels of adipogenic transcriptional factors, including C/EBPα, C/EBPβ and PPARγ, and subsequently significantly decreased levels of lipid accumulation related genes (FABP4 and FAS) compared with those of control. In contrast, overexpression of LKB1 promoted thermogenic and lipolysis related genes in yak adipocyte, including PGC1α, PPARα, UCP1, ATGL, HSL and LPL. Therefore, these results would provide new insights to decipher the network for domestic yak adipose deposition, and LKB1 might be as a new molecular target for animal environmental-resistant breeding.