Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

Abstract

In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin‐like protein 4 (ANGPTL4) is a well‐known downstream target of peroxisome proliferator‐activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very‐low‐density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two‐step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

Unveiling the Genetic Landscape of Feed Efficiency in Holstein Dairy Cows: Insights into Heritability, Genetic Markers, and Pathways via Meta-Analysis

“…One study reported that the abundance of angiopoietin-like protein 4 (ANGPTL4) mRNA was increased in all three models of declining EB, suggesting that ANGPTL4 may act as an early autocrine/paracrine or endocrine signal to influence energy status in lactating cattle ( Koltes and Spurlock, 2012 ). Kong et al (2020) reported that ANGPTL4 promotes the transport of triglycerides in the form of very low-density lipoprotein, contributing to the adaptive regulation of the lipid transport system in dairy cattle. Some studies have reported that ANGPTL4 is associated with perinatal fatty liver, ketosis, and other metabolic disorders in dairy cows ( Wang et al, 2018 ; Kong et al, 2020 ).…”

FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling

“…ApoB, ApoE, MTTP, and LDLR are the main structural and/or regulatory proteins for the assembly and transport of liver VLDL. Their expression promotes the synthesis and secretion of VLDL from the liver and reduces liver fat content [ 22 , 45 , 46 ]. ApoE gene deletion results in the blocked synthesis of TG-rich VLDL and fat accumulation in the liver.…”

“…After anesthetic treatment using thiamylal sodium, the caudate liver lobe of newborn calves was obtained under aseptic conditions within 24 h. Subsequently, hepatocytes were isolated using a modified 2-step collagenase perfusion method, as described previously [ 19 , 20 ]. Perfusion A (140 mmol/L NaCl, 6.7 mmol/L KCl, 10 mmol/L HEPES, 0.5 mmol/L EDTANa 2 and 2.5 mmol/L glucose; pH 7.2–7.4, 37 °C), perfusion B (140 mmol/L NaCl, 6.7 mmol/L KCl, 30 mmol/L HEPES, 5 mmol/L CaCl 2 , and 2.5 mmol/L glucose; pH 7.2–7.4, 37 °C), and perfusion C (0.2 g/L collagenase IV (Gibco; Gaithersburg, MD, USA) in perfusion B, pH 7.2–7.4, 37 °C) were used [ 21 , 22 ]. After terminating collagenase digestion, the tissue was cut into smaller pieces to release the hepatocytes.…”

Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease

“…Key lipid synthesis-associated transcripts, which include Fasn and Acc1, did not show any significant changes across the experimental groups. However, the expression of Angptl4, which can promote triglyceride clearance in hepatocytes [21], showed a decrease of over 2-fold in the ETOH-BKO mice compared to the ETOH-WT mice. Meanwhile, the transcript levels of Cyp7A1, a key gene for bile acid synthesis, were increased in the PF-BKO group compared to the PF-WT group.…”