+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Hepatic methionine homeostasis is conserved in C57BL/6N mice on high-fat diet despite major changes in hepatic one-carbon metabolism

Hepatic methionine homeostasis is conserved in C57BL/6N mice on high-fat diet despite major changes in hepatic one-carbon metabolism

Plos one 8(3): E57387

Obesity is an underlying risk factor in the development of cardiovascular disease, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). Increased hepatic lipid accumulation is a hallmark in the progression of NAFLD and impairments in liver phosphatidylcholine (PC) metabolism may be central to the pathogenesis. Hepatic PC biosynthesis, which is linked to the one-carbon (C1) metabolism by phosphatidylethanolamine N-methyltransferase, is known to be important for hepatic lipid export by VLDL particles. Here, we assessed the influence of a high-fat (HF) diet and NAFLD status in mice on hepatic methyl-group expenditure and C1-metabolism by analyzing changes in gene expression, protein levels, metabolite concentrations, and nuclear epigenetic processes. In livers from HF diet induced obese mice a significant downregulation of cystathionine β-synthase (CBS) and an increased betaine-homocysteine methyltransferase (BHMT) expression were observed. Experiments in vitro, using hepatoma cells stimulated with peroxisome proliferator activated receptor alpha (PPARα) agonist WY14,643, revealed a significantly reduced Cbs mRNA expression. Moreover, metabolite measurements identified decreased hepatic cystathionine and L-α-amino-n-butyrate concentrations as part of the transsulfuration pathway and reduced hepatic betaine concentrations, but no metabolite changes in the methionine cycle in HF diet fed mice compared to controls. Furthermore, we detected diminished hepatic gene expression of de novo DNA methyltransferase 3b but no effects on hepatic global genomic DNA methylation or hepatic DNA methylation in the Cbs promoter region upon HF diet. Our data suggest that HF diet induces a PPARα-mediated downregulation of key enzymes in the hepatic transsulfuration pathway and upregulates BHMT expression in mice to accommodate to enhanced dietary fat processing while preserving the essential amino acid methionine.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053514989

Download citation: RISBibTeXText

PMID: 23472083

DOI: 10.1371/journal.pone.0057387

Related references

Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic autophagy. Food and Chemical Toxicology 121: 283-296, 2018

Lactoferrin attenuates high-fat diet-induced hepatic steatosis and lipid metabolic dysfunctions by suppressing hepatic lipogenesis and down-regulating inflammation in C57BL/6J mice. Food and Function 9(8): 4328-4339, 2018

Contribution of Hepatic Retinaldehyde Dehydrogenase Induction to Impairment of Glucose Metabolism by High-Fat-Diet Feeding in C57BL/6J Mice. Basic and Clinical Pharmacology and Toxicology 123(5): 539-548, 2018

Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice. Molecular Nutrition and Food Research 58(7): 1502-1512, 2014

The effect of fasting on hepatic lipid accumulation and transcriptional regulation of lipid metabolism differs between C57BL/6J and BALB/cA mice fed a high-fat diet. Toxicologic Pathology 36(6): 850-857, 2008

GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by improving hepatic energy metabolism in high-fat diet fed mice. Molecular and Cellular Endocrinology 474: 227-237, 2018

High-Fructose Intake Impairs the Hepatic Hypolipidemic Effects of a High-Fat Fish-Oil Diet in C57BL/6 Mice. Journal of Clinical and Experimental Hepatology 6(4): 265-274, 2016

Effect of high-intensity intermittent exercise on high-fat diet-induced hepatic fat deposition in C57BL/6 mice. Zhonghua Gan Zang Bing Za Zhi 27(4): 312-315, 2019

Dietary Starfish Oil Prevents Hepatic Steatosis and Hyperlipidemia in C57BL/6N Mice Fed High-fat Diet. Journal of Oleo Science 66(7): 761-769, 2017

Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice. Nutrition Research and Practice 7(4): 294-301, 2013

Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet. Plos one 13(8): E0201310, 2018

Preventative effects of Platycodon grandiflorum treatment on hepatic steatosis in high fat diet-fed C57BL/6 mice. Biological & Pharmaceutical Bulletin 33(3): 450-454, 2010

Chestnut inner shell extract inhibits development of hepatic steatosis in C57BL/6 mice fed a high-fat diet. Food Chemistry1: 2, 437-442, 2010

Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance. Molecular and Cellular Biology 36(21): 2715-2727, 2016

Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice. Metabolism: Clinical and Experimental 64(2): 305-314, 2015