TY - JOUR T1 - Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice A1 - Ohn, Jung Hun A1 - Hwang, Ji Yeon A1 - Moon, Min Kyong A1 - Ahn, Hwa Young A1 - Kim, Hwan Hee A1 - Koo, Young Do A1 - Kim, Kwang-Il A1 - Chang, Hyuk Jae A1 - Lee, Hye Seung A1 - Jang, Hak Chul A1 - Park, Young Joo Y1 - 2017/10/10 N2 - The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) γ 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 PPARγ1 and PPARα 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 PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα 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. JF - PLOS ONE JA - PLOS ONE VL - 12 IS - 10 UR - https://doi.org/10.1371/journal.pone.0186021 SP - e0186021 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0186021 ER -