IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle
Mitochondrial NADP<sup>+</sup>-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP<sup>+</sup> to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/16/5596 |
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| author | Jeong Hoon Pan Jingsi Tang Young Jun Kim Jin Hyup Lee Eui-Cheol Shin Jiangchao Zhao Kee-Hong Kim Kyung A. Hwang Yan Huang Jae Kyeom Kim |
| author_facet | Jeong Hoon Pan Jingsi Tang Young Jun Kim Jin Hyup Lee Eui-Cheol Shin Jiangchao Zhao Kee-Hong Kim Kyung A. Hwang Yan Huang Jae Kyeom Kim |
| author_sort | Jeong Hoon Pan |
| collection | DOAJ |
| description | Mitochondrial NADP<sup>+</sup>-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP<sup>+</sup> to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle development and fatty acid metabolism. Here, we examined the effects of IDH2 knockout (KO) on skeletal muscle energy homeostasis. Calf skeletal muscle samples from 10-week-old male IDH2 KO and wild-type (WT; C57BL/6N) mice were harvested, and the ratio of skeletal muscle weight to body and the ratio of mitochondrial to nucleic DNA were measured. In addition, genes involved in myogenesis, mitochondria biogenesis, adipogenesis, and thermogenesis were compared. Results showed that the ratio of skeletal muscle weight to body weight was lower in IDH2 KO mice than those in WT mice. Of note, a noticeable shift in fiber size distribution was found in IDH2 KO mice. Additionally, there was a trend of a decrease in mitochondrial content in IDH2 KO mice than in WT mice (<i>p</i> = 0.09). Further, mRNA expressions for myogenesis and mitochondrial biogenesis were either decreased or showed a trend of decrease in IDH2 KO mice. Moreover, genes for adipogenesis pathway (<i>Pparg</i>, <i>Znf423</i>, and <i>Fat1</i>) were downregulated in IDH2 KO mice. Interestingly, mRNA and protein expression of uncoupling protein 1 (UCP1), a hallmark of thermogenesis, were remarkably increased in IDH2 KO mice. In line with the UCP1 expression, IDH2 KO mice showed higher rectal temperature than WT mice under cold stress. Taken together, IDH2 deficiency may affect myogenesis, possibly due to impairments of muscle generation and abnormal fatty acid oxidation as well as thermogenesis in muscle via upregulation of UCP1. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:57:43Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-358d4216f2754ddba7ea84e18132617d2023-11-20T09:07:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116559610.3390/ijms21165596IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal MuscleJeong Hoon Pan0Jingsi Tang1Young Jun Kim2Jin Hyup Lee3Eui-Cheol Shin4Jiangchao Zhao5Kee-Hong Kim6Kyung A. Hwang7Yan Huang8Jae Kyeom Kim9Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE 19716, USADepartment of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USADepartment of Food and Biotechnology, Korea University, Sejong 30019, KoreaDepartment of Food and Biotechnology, Korea University, Sejong 30019, KoreaDepartment of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, KoreaDepartment of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USADepartment of Food Science, Purdue University, West Lafayette, IN 47897, USADepartment of Agrofood Resources, National Institute of Agricultural Sciences, Rural Development Administration, Jeollabuk-do 55365, KoreaDepartment of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USADepartment of Behavioral Health and Nutrition, University of Delaware, Newark, DE 19716, USAMitochondrial NADP<sup>+</sup>-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP<sup>+</sup> to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle development and fatty acid metabolism. Here, we examined the effects of IDH2 knockout (KO) on skeletal muscle energy homeostasis. Calf skeletal muscle samples from 10-week-old male IDH2 KO and wild-type (WT; C57BL/6N) mice were harvested, and the ratio of skeletal muscle weight to body and the ratio of mitochondrial to nucleic DNA were measured. In addition, genes involved in myogenesis, mitochondria biogenesis, adipogenesis, and thermogenesis were compared. Results showed that the ratio of skeletal muscle weight to body weight was lower in IDH2 KO mice than those in WT mice. Of note, a noticeable shift in fiber size distribution was found in IDH2 KO mice. Additionally, there was a trend of a decrease in mitochondrial content in IDH2 KO mice than in WT mice (<i>p</i> = 0.09). Further, mRNA expressions for myogenesis and mitochondrial biogenesis were either decreased or showed a trend of decrease in IDH2 KO mice. Moreover, genes for adipogenesis pathway (<i>Pparg</i>, <i>Znf423</i>, and <i>Fat1</i>) were downregulated in IDH2 KO mice. Interestingly, mRNA and protein expression of uncoupling protein 1 (UCP1), a hallmark of thermogenesis, were remarkably increased in IDH2 KO mice. In line with the UCP1 expression, IDH2 KO mice showed higher rectal temperature than WT mice under cold stress. Taken together, IDH2 deficiency may affect myogenesis, possibly due to impairments of muscle generation and abnormal fatty acid oxidation as well as thermogenesis in muscle via upregulation of UCP1.https://www.mdpi.com/1422-0067/21/16/5596IDH2 knockoutskeletal musclemyogenesismitochondrial biogenesisfatty acid oxidationUCP1 |
| spellingShingle | Jeong Hoon Pan Jingsi Tang Young Jun Kim Jin Hyup Lee Eui-Cheol Shin Jiangchao Zhao Kee-Hong Kim Kyung A. Hwang Yan Huang Jae Kyeom Kim IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle International Journal of Molecular Sciences IDH2 knockout skeletal muscle myogenesis mitochondrial biogenesis fatty acid oxidation UCP1 |
| title | IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle |
| title_full | IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle |
| title_fullStr | IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle |
| title_full_unstemmed | IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle |
| title_short | IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle |
| title_sort | idh2 deficiency is critical in myogenesis and fatty acid metabolism in mice skeletal muscle |
| topic | IDH2 knockout skeletal muscle myogenesis mitochondrial biogenesis fatty acid oxidation UCP1 |
| url | https://www.mdpi.com/1422-0067/21/16/5596 |
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