Small heterodimer partner

The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) [gamma] expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing...

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Bibliographic Details
Published in:PloS one 2017-10, Vol.12 (10), p.e0186021
Main Authors: Ohn, Jung Hun, Hwang, Ji Yeon, Moon, Min Kyong, Ahn, Hwa Young, Kim, Hwan Hee, Koo, Young Do, Kim, Kwang-Il, Chang, Hyuk Jae, Lee, Hye Seung, Jang, Hak Chul, Park, Young Joo
Format: Article
Language:English
Subjects:
Gene expression
Genetic aspects
Lipid metabolism
Myocardial diseases
Physiological aspects
Prevention
Risk factors
Online Access:Get full text
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Summary:The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) [gamma] expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0.05). Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPAR[gamma]1 and PPAR[alpha] were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPAR[gamma]. We confirmed the reduced expression of PPAR[gamma]1 and PPAR[alpha] target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0186021