Choline and methionine regulate lipid metabolism via the AMPK signaling pathway in hepatocytes exposed to high concentrations of nonesterified fatty acids

Abstract

High concentrations of nonesterified fatty acids (NEFAs) and β‐hydroxybutyric acid (BHBA) induce lipid peroxidation, resulting in liver damage. Choline and methionine (Met) can promote energy balance and benefit liver health in transition dairy cows; however, the regulating mechanism remains unclear. In the present study, we established the hepatocyte damage model by 1.5 mM NEFAs or BHBA treatment, and examined lipid metabolism in hepatocytes. The results showed that 1.5 mM NEFAs and 1.5 mM BHBA significantly decreased the messenger RNA (mRNA) expression of AMP‐activated protein kinase (AMPK)‐α as well as its target genes carnitine palmitoyltransferase‐1α (CPT‐1α), acetyl‐CoA carboxylase, fatty acid synthetase, and Apolipoprotein B100 (ApoB100). Choline and Met upregulated the phosphorylation level of AMPK‐α, which was blocked by BML (an AMPK‐α inhibitor). The mRNA expression level of peroxisome proliferator‐activated receptor‐α (PPAR‐α), CPT‐1α, and ApoB100 showed a similar trend. The expressions of liver X recptoer α (LXR‐α) and sterol regulatory element‐binding protein 1c (SREBP‐1c) were decreased by choline and Met, while only the decrease of LXR‐α was blocked by BML. These findings indicate that the high‐level NEFAs and BHBA weaken the lipid metabolism by impairing the fatty acid oxidation, synthesis, and transport proteins. Choline and Met regulate PPAR‐α and LXR‐α transcriptional activity through AMPK‐α phosphorylation and regulate SREBP‐1c independently of AMPK‐α to promote lipid oxidation and transport in NEFAs‐treated hepatocytes.

Identification and characterization of dairy cows with different backfat thickness antepartum in relation to postpartum loss of backfat thickness: A cluster analytic approach

“…The MET treatment did not affect performance and health status, as reported previously (Süss et al, 2019). Considering that MET is involved in one-carbon metabolism (Vailati-Riboni et al, 2020) and regulates lipid metabolism via the AMPK pathway to increase lipid oxidation in NEFAtreated hepatocytes (Shen et al, 2020), MET might affect lipid metabolism in dairy cows. The portion of hyperketotic cows (≥1.2 mmol/L BHB) from the basic trial, with a total of 1,709 cows, was not different in the control and the MET-supplemented group (11.7% vs. 12.3%); furthermore, the proportions of cows with BFT <14 mm were the same in both groups (81.9% and 82.6%, respectively; Süss et al, 2019).…”

The Dynamic Transcription Profiles of Proliferating Bovine Ovarian Granulosa When Exposed to Increased Levels of β-Hydroxybutyric Acid

“…Hence, low doses of BHBA have been shown to exert positive effects in the treatment of certain diseases (33,34). However, if the concentration of BHBA increases excessively, this could directly or indirectly affect normal liver metabolism (35,36) and reproductive performance (e.g., granulosa cell development and oocyte maturation) (20,37,38) in ruminants such as cows.…”

SIRT2 Deficiency Aggravates Diet-Induced Nonalcoholic Fatty Liver Disease through Modulating Gut Microbiota and Metabolites

“…In addition, the activated glycerophospholipids metabolism pathway can effectively alleviate hypercholesterolemia and obesity-related complications [32]. Dysfunction of choline metabolism, adrenergic signaling, and glycerophospholipid metabolism could lead to a range of metabolism-related diseases, including NASH [33]. Specifically speaking, the differential metabolites enriched in these hepatoprotective pathways performed NAFLD-inhibition functions.…”