Abstract
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced ART and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500 mu M/100 nM). In addition, SHP overexpression increased Socs3 mRNA and reduced IRS-1 protein levels. SHP overexpression also induced Cd36 expression (similar to 6.2 fold; p
Original language | English |
---|---|
Pages (from-to) | 541-551 |
Number of pages | 11 |
Journal | Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids |
Volume | 1862 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2017 |
Keywords
- Insulin resistance
- Diabetic cardiomyopathy
- Nuclear receptors
- Small heterodimer partner
- ORPHAN NUCLEAR RECEPTOR
- FATTY-ACID TRANSPORT
- FACTOR-KAPPA-B
- ACTIVATED RECEPTOR
- CARDIAC-HYPERTROPHY
- HEPATIC GLUCONEOGENESIS
- DOWN-REGULATION
- HEART-DISEASE
- MOUSE MODELS
- MUSCLE-CELLS