Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China.
Cell Biochem Biophys. 2013;67(3):1157-69. doi: 10.1007/s12013-013-9629-1.
Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation through up-regulating the protein levels of liver kinase B1. Activated AMPKα increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα). NEFAs also directly activate the PPARα independent of AMPKα. Activated PPARα increased the lipolytic genes expression to increase lipid oxidation. Furthermore, activated AMPKα inhibited the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid synthesis. Activated AMPKα phosphorylated and inhibited acetyl-CoA carboxylase and increased carnitine palmitoyltransferase-1 activity, which increased lipid oxidation. Consequently, the triglyceride content in the NEFAs-treated hepatocytes was significantly decreased. These results indicate that NEFAs activate the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in hepatocytes, which in turn, generates more ATP to relieve the negative energy balance in transition dairy cows.
非酯化脂肪酸 (NEFAs) 作为信号分子，参与调节基因表达，从而调节脂肪代谢。然而，NEFAs 对奶牛脂质代谢的调节机制尚不清楚。AMP 激活的蛋白激酶 (AMPK) 信号通路在调节肝脏脂质代谢中起着关键作用。在体外，培养牛肝细胞并分别用不同浓度的 NEFAs 和 AMPKα 抑制剂 (BML-275) 处理。NEFAs 通过上调肝激酶 B1 的蛋白水平来增加 AMPKα 的磷酸化。激活的 AMPKα 增加过氧化物酶体增殖物激活受体 α (PPARα) 的表达和转录活性。NEFAs 也可以独立于 AMPKα 直接激活 PPARα。激活的 PPARα 增加脂肪分解基因的表达，以增加脂肪氧化。此外，激活的 AMPKα 抑制固醇调节元件结合蛋白 1c 和碳水化合物反应元件结合蛋白的表达和转录活性，从而降低脂肪生成基因的表达，减少脂质合成。激活的 AMPKα 磷酸化并抑制乙酰辅酶 A 羧化酶，增加肉碱棕榈酰转移酶-1 的活性，从而增加脂肪氧化。因此，NEFAs 处理的肝细胞中的甘油三酯含量显著降低。这些结果表明，NEFAs 通过激活 AMPKα 信号通路，增加肝细胞中的脂肪氧化和减少脂肪合成，从而产生更多的 ATP 来缓解泌乳过渡期奶牛的负能平衡。
