Abstract
The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. 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 sodium acetate (neutralized acetic acid) and BML-275 (an AMPKα inhibitor). Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.
Highlights
The mechanism of carbohydrate digestion and nutrient metabolism in ruminants differs significantly from that in monogastric animals
Acetic acid activates AMPKa in hepatocytes To determine the effect of acetic acid on the AMPKa, we determined the AMP and ATP content, the AMPKa phosphorylation and activity, and the liver kinase B1 (LKB1) protein expression
The phosphorylation level of AMPKa and AMPKa activity was significantly higher in the acetate-treated groups than in the control group and was significantly lower in the BML-275 and BML-275+acetate groups than in the control group (Fig. 2G, 2H; p,0.05 and p,0.01). These results demonstrate that acetic acid converts to acetyl-CoA with the consumption of ATP, resulting in a significant increase in the AMP/ATP ratio, which induces an increase of AMPKa phosphorylation and activity
Summary
The mechanism of carbohydrate digestion and nutrient metabolism in ruminants differs significantly from that in monogastric animals. Cellulose and starch are the main carbohydrates for ruminants. Ruminal micro-organisms convert cellulose and starch to volatile fatty acids (VFAs, including acetic acid, propionic acid, and butyric acid), carbon dioxide, and methane. The blood acetate concentration in dairy cows is 3.6 mM, which is dozens of times higher than that in monogastric animals [2]. The biological function of acetic acid in dairy cows is different from that in humans and mice. Acetic acid is mainly used for milk fat synthesis in dairy cows [2]. In humans and mice, acetic acid is mainly used to generate energy through tricarboxylic acid cycle in hepatocytes [3]. It has become evident that acetic acid can act as a signaling molecule to regulate gene expression in the liver [4]
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