Journal Article

Myocardial metabolic alterations in mice with diet-induced atherosclerosis: linking sulfur amino acid and lipid metabolism

Nami Kim, Jueun Lee, Geum-Sook Hwang, Sunhee Jung, Do Hyun Ryu, Min Jeong Shin

2017

Overview

Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the effect of diet on the atherosclerotic heart’s metabolism is unclear. We used an integrated metabolomics and lipidomics approach to evaluate metabolic perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8, 16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice were quantitatively verified using liquid chromatography-mass spectrometry (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG) levels in the AD group were altered depending on the degree of unsaturation. Additionally, levels of SCD1, SREBP-1, and PPARγ were reduced in AD mice after 25 weeks, while levels of reactive oxygen species were elevated. The results suggest that a long-term AD leads to SAA metabolism dysregulation and increased oxidative stress in the heart, causing SCD1 activity suppression and accumulation of toxic TGs with a low degree of unsaturation. These findings demonstrate that the SAA metabolic pathway is a promising therapeutic target for CVD treatment and that metabolomics can be used to investigate the metabolic signature of atherosclerosis.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group
• Subject: 140/131 / 631/1647/320 / 631/45/320 / 631/45/608 / Amino acid sequence / Amino Acids / Amino Acids - chemistry / Amino Acids - metabolism / Animals / Arteriosclerosis / Atherogenic diet / Atherosclerosis / Atherosclerosis - etiology / Atherosclerosis - metabolism / Cardiovascular diseases / Chromatography, Liquid / Diet / Diet, Atherogenic / Diet, Atherogenic - adverse effects / Heart / Humanities and Social Sciences / Lipid Metabolism / Lipids / Lipids - blood / Liquid chromatography / Magnetic Resonance Spectroscopy / Male / Mass spectrometry / Mass spectroscopy / Metabolism / Metabolomics / Mice, Inbred C57BL / multidisciplinary / Myocardium / Myocardium - metabolism / NMR / Nuclear magnetic resonance / Oxidative metabolism / Oxidative Stress / Reactive oxygen species / Science / Science (multidisciplinary) / Stearoyl-CoA Desaturase / Stearoyl-CoA Desaturase - metabolism / Sterol regulatory element-binding protein / Sulfur / Tandem Mass Spectrometry / Therapeutic applications