Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes

Abstract

Adiponectin (Ad) plays a crucial role in hepatic lipid metabolism. However, the regulating mechanism of hepatic lipid metabolism by Ad in dairy cows is unclear. Hepatocytes from a newborn female calf were cultured in vitro and treated with different concentrations of Ad and BML-275 (an AMPKα inhibitor). The results showed that Ad significantly increased the expression of two Ad receptors. Furthermore, the phosphorylation and activity of AMPKα, as well as the expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) and its target genes involved in lipid oxidation, showed a corresponding trend of upregulation. However, the expression levels and transcriptional activity of sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) decreased in a similar manner. When BML-275 was added, the p-AMPKα level as well as the expression and activity of PPARα and its target genes were significantly decreased. However, the expression levels of SREBP-1c, ChREBP and their target genes showed a trend of upregulation. Furthermore, the triglyceride (TG) content was significantly decreased in the Ad-treated groups. These results indicate that Ad activates the AMPK signaling pathway and mediates lipid metabolism in bovine hepatocytes cultured in vitro by promoting lipid oxidation, suppressing lipid synthesis and reducing hepatic lipid accumulation.

Keywords: ACCα; ACO; ACSL-1; AMP-activated protein kinase; AMPK; AMPK signaling pathways; Ad; AdipoR1; AdipoR2; Adiponectin; Bovine hepatocytes; CPT-1; CPT-2; ChREBP; EMSA; FAS; L-FABP; Lipid oxidation; Lipid synthesis; NEB; PPARα; SCD-1; SREBP-1c; TG; acetyl-CoA carboxylase α; acyl-CoA oxidase; acyl-CoA synthetase long-chain 1; adiponectin; adiponectin receptor 1; adiponectin receptor 2; carbohydrate responsive element-binding protein; carnitine palmitoyltransferase 1; carnitine palmitoyltransferase 2; electrophoretic mobility shift assay; fatty acid synthase; liver fatty acid-binding protein; negative energy balance; p-AMPKα; peroxisome proliferator-activated receptor α; phosphorylated-AMPKα; stearoyl-CoA desaturase 1; sterol regulatory element-binding protein 1c; triglyceride.