Key result
Insulin induces triglyceride accumulation in cow hepatocytes by inhibiting AMPKα signaling.
Why the study?
The mechanism by which insulin regulates lipid metabolism and contributes to hepatic fat accumulation in dairy cows with type II ketosis is not completely clear.
Does insulin regulate lipid metabolism via the AMPK signaling pathway in primary cultured cow hepatocytes?
Does insulin regulate lipid metabolism via the AMPK signaling pathway in primary cultured cow hepatocytes?
Insulin induces hepatic fat accumulation in cow hepatocytes by suppressing the AMPKα signaling pathway, providing a mechanistic link between hyperinsulinemia and type II ketosis in dairy cows.
Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.
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Li et al. (2018) studied Hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis. Insulin vs. Absence of insulin / presence or absence of AICAR was evaluated on Lipid metabolism regulation (AMPKα phosphorylation, gene/protein expression, triglyceride content). Insulin inhibited the AMPKα signaling pathway in cow hepatocytes, increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly, thereby inducing triglyceride accumulation.
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