Non-esterified fatty acids promote expression and secretion of angiopoietin-like protein 4 in calf hepatocytes cultured in vitro

Abstract

An elevated plasma non-esterified fatty acids (NEFA) concentration is an important indicator of negative energy balance, which is often associated with metabolic diseases such as fatty liver and ketosis. Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine that plays important roles in the regulation of lipid metabolism. However, the direct effects of high concentrations of NEFA on ANGPTL4 expression and secretion in hepatocytes from cows are not entirely clear. The objective of this study was to investigate the effects of different NEFA concentrations on ANGPTL4 expression and secretion in calf hepatocytes cultured in vitro. NEFA was added to the culture solution at final concentrations of 0.6, 1.2, 1.8, and 2.4 mmol/L. After 24 h of continuous culture, ANGPTL4 mRNA and protein expression levels in the hepatocytes were determined by real-time polymerase chain reaction and western blot, respectively. ANGPTL4 secretion in the supernatant was determined by enzyme-linked immunosorbent assay. The results showed similar levels of ANGPTL4 expression and secretion following treatment with 0.6 and 1.2 mmol/L NEFA, which were higher than those observed for the controls (P < 0.05). ANGPTL4 expression and secretion were also similar at 1.8 and 2.4 mmol/L NEFA and significantly higher than those observed for controls (P < 0.01). These data suggest that high concentrations of NEFA significantly promote ANGPTL4 expression and secretion in bovine hepatocytes. In particular, this promotion occurs in a dose-dependent manner and may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period.

Comparative genome-wide methylation analysis of longissimus dorsi muscles between Japanese black (Wagyu) and Chinese Red Steppes cattle

“…ANGPTL4 is mainly expressed in liver and adipose tissues [38] and plays important roles in the regulation of lipid metabolism. Previous studies have suggested that a SNP in ANGPTL4 is associated with intramuscular fat [39] and the expression level of ANGPTL4 affects meat quality traits of pigs [40]. Recent studies have shown that acyl-CoA synthetase family member 3 (ACSF3), in which DMRs in promoter region were found in the present study to be negatively correlated with the gene expression level, plays a critical role in mammal fatty acid synthesis in mitochondrion [41].…”

α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression

“…The expression of Angptl4 is also regulated through a synergistic induction of the lipid-sensing peroxisome proliferator-activated receptors (PPARs) α, β, and γ (40). Among the lipids, fatty acids (FA) are the best-recognized inducers of Angptl4 expression (16, 41-43). Although FA are an energy source, they are also recognized as regulators of inflammation, and it has been suggested that PPARs play an important role in FA-dependent gene regulation (44).…”

High non‐esterified fatty acid concentrations promote expression and secretion of fibroblast growth factor 21 in calf hepatocytes cultured in vitro

“…All experimental procedures were approved by the Institutional Animal Care and Use Committee of Northwest A&F University, Yangling, People's Republic of China. Hepatocytes were isolated using the collagenase perfusion method as previously described (Wang et al., ; Zhang et al., ). For each isolation procedure, the liver (caudate process) was obtained under sterile conditions from a neonatal Holstein calf (male) anesthetized with thiamylal sodium.…”