Expression patterns of hepatic genes involved in lipid metabolism in cows with subclinical or clinical ketosis

ABSTRACT Dairy cows with ketosis are characterized by high blood concentrations of ketone bodies and hepatic lipid metabolism disorder. The discrepancies in the abundance of mRNA encoding a variety of hepatic candidate genes in varying degrees of ketotic cows represent specific responses of the liver to the challenge of fatty acids and ketone bodies. Importantly, the expression disorder of hepatic genes involved in lipid metabolism plays a promoting role in the onset and progression of ketosis. Thus, the aim of this study was to investigate the expression patterns of genes involved in the hepatic fatty acids uptake, transport, activation, β-oxidation, synthesis, and esterification in the cows with subclinical ketosis (SCK) or clinical ketosis (CK). Twenty-four cows were selected into control [n = 8, β-hydroxybutyrate (BHB) ≤0.6 mM], SCK (n = 8, 3.0 > BHB ≥ 1.2 mM), and CK (n = 8, BHB ≥3.0 mM) groups according to the blood BHB concentration and clinical symptoms. The accumulation of hepatic lipid, as indicated by triglycerides (TG) contents and Oil Red O and hematoxylin and eosin staining, was pronouncedly exacerbated in the tCK group compared with the control and SCK groups. The hepatic mRNA expression of fatty acids transport and activation genes, liver fatty acid-binding protein (FABP1) and long-chain acyl-CoA synthetase 1 (ACSL1), were both significantly higher in the SCK and CK groups than in the control group. The expression levels of peroxisome proliferator-activated receptor α (PPARA) and its target genes, carnitine palmitoyltransferase 1A (CPT1A) and carnitine palmitoyltransferase 2 (CPT2), were significantly elevated in the SCK group but reduced in the CK group compared with control group. Furthermore, the gene expression level of sterol regulatory element-binding protein 1 (SREBP1) and the protein expression level of sterol regulatory element-binding protein 1c and its target genes acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD1) and TG synthesis genes diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) were significantly higher in the CK group relative to the control group. In short, the present data indicated that hepatic fatty acids uptake, transport, and activation are significantly increased in cows with SCK and CK, hepatic fatty acids β-oxidation is significantly increased in SCK cows but markedly decreased in CK cows, and hepatic fatty acids and TG synthesis are significantly increased in CK cows, thereby inducing hepatic steatosis in CK cows.