Premium
Disturbances in Cardiac Glutathione Augments Cardiac Lipotoxicity in Mice with Diet‐Induced Obesity
Author(s) -
Ghosh Sanjoy,
Sulistyoningrum Dian,
Glier Melissa B,
Devlin Angela M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.547.12
Subject(s) - endocrinology , medicine , glutathione , lipotoxicity , triglyceride , chemistry , lipogenesis , cystathionine beta synthase , adipose tissue , obesity , biology , insulin resistance , biochemistry , cysteine , cholesterol , enzyme
Cardiac lipid accumulation is a key feature of obesity‐related cardiomyopathy. The role of the antioxidant glutathione (GSH) in cardiolipotoxicity is unclear. Cystathionine‐β‐synthase(Cbs) provides 50% of total cysteine required for GSH biosynthesis in the liver. We studied the effect of diet‐induced obesity in mice heterozygous for targeted deletion of Cbs(+/−) and C57BL6/J (+/+) mice fed a high fat (60% energy) diet (HF) or a control diet (C) from weaning for 12 weeks. HF+/− and HF+/+ mice had higher body weight (P<0.001) and adipose tissue accumulation (P<0.001) than C+/− and C+/+ mice. Total GSH and reduced GSH levels in heart were lower in +/− mice (P<0.01) than in +/+ mice and where further reduced in +/− mice fed the HF diet. This was accompanied by higher levels of triglyceride and higher levels of nitrotyrosine in heart form HF+/− mice. Expression of genes (mRNA) related to fatty acid oxidation ( Acox1 , Ppara ) and mitochondrial function ( Pgc1a , Nrf1 , Rela ) were higher (P<0.01) in heart from +/− mice than in +/+ mice. Feeding the HF diet had no effect on gene expression in the +/+ mice but reduced levels of mRNA in +/− mice. This study demonstrates a potential role between Cbs, heart GSH levels, and triglyceride accumulation in heart during diet‐induced obesity.