Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice

Jung Hun Ohn, Ji Yeon Hwang, Min Kyong Moon, Hwa Young Ahn, Hwan Hee Kim, Young Do Koo, Kwang Il Kim, Hyuk-Jae Chang, Hye Seung Lee, Hak Chul Jang, Young Joo Park

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere0186021
JournalPLoS One
Volume12
Issue number10
DOIs
Publication statusPublished - 2017 Oct 1

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Peroxisome Proliferator-Activated Receptors
High Fat Diet
high fat diet
Nutrition
myocardium
Myocardium
Fats
Lipids
Knockout Mice
Genes
mice
acyl-CoA dehydrogenase
Long-Chain Acyl-CoA Dehydrogenase
Microarrays
lipids
Gene expression
Lipogenesis
Acyl-CoA Dehydrogenase
lipogenesis
Cell growth

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ohn, J. H., Hwang, J. Y., Moon, M. K., Ahn, H. Y., Kim, H. H., Koo, Y. D., ... Park, Y. J. (2017). Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice. PLoS One, 12(10), [e0186021]. https://doi.org/10.1371/journal.pone.0186021
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. / Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice. In: PLoS One. 2017 ; Vol. 12, No. 10.
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abstract = "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.",
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Ohn, JH, Hwang, JY, Moon, MK, Ahn, HY, Kim, HH, Koo, YD, Kim, KI, Chang, H-J, Lee, HS, Jang, HC & Park, YJ 2017, 'Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice', PLoS One, vol. 12, no. 10, e0186021. https://doi.org/10.1371/journal.pone.0186021

Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice. / 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.

In: PLoS One, Vol. 12, No. 10, e0186021, 01.10.2017.

Research output: Contribution to journalArticle

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T1 - Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice

AU - Ohn, Jung Hun

AU - Hwang, Ji Yeon

AU - Moon, Min Kyong

AU - Ahn, Hwa Young

AU - Kim, Hwan Hee

AU - Koo, Young Do

AU - Kim, Kwang Il

AU - Chang, Hyuk-Jae

AU - Lee, Hye Seung

AU - Jang, Hak Chul

AU - Park, Young Joo

PY - 2017/10/1

Y1 - 2017/10/1

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.

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