Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver.
We recently identified a nuclear-encoded miRNA (miR-181c) in cardiomyocytes that can translocate into mitochondria to regulate mitochondrial gene mt-COX1 and influence obesity-induced cardiac dysfunction through the mitochondrial pathway. Because liver plays a pivotal role during obesity, we hypothe...
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0256973&type=printable |
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| author | Kei Akiyoshi Gretha J Boersma Miranda D Johnson Fernanda Carrizo Velasquez Brittany Dunkerly-Eyring Shannon O'Brien Atsushi Yamaguchi Charles Steenbergen Kellie L K Tamashiro Samarjit Das |
| author_facet | Kei Akiyoshi Gretha J Boersma Miranda D Johnson Fernanda Carrizo Velasquez Brittany Dunkerly-Eyring Shannon O'Brien Atsushi Yamaguchi Charles Steenbergen Kellie L K Tamashiro Samarjit Das |
| author_sort | Kei Akiyoshi |
| collection | DOAJ |
| description | We recently identified a nuclear-encoded miRNA (miR-181c) in cardiomyocytes that can translocate into mitochondria to regulate mitochondrial gene mt-COX1 and influence obesity-induced cardiac dysfunction through the mitochondrial pathway. Because liver plays a pivotal role during obesity, we hypothesized that miR-181c might contribute to the pathophysiological complications associated with obesity. Therefore, we used miR-181c/d-/- mice to study the role of miR-181c in hepatocyte lipogenesis during diet-induced obesity. The mice were fed a high-fat (HF) diet for 26 weeks, during which indirect calorimetric measurements were made. Quantitative PCR (qPCR) was used to examine the expression of genes involved in lipid synthesis. We found that miR-181c/d-/- mice were not protected against all metabolic consequences of HF exposure. After 26 weeks, the miR-181c/d-/- mice had a significantly higher body fat percentage than did wild-type (WT) mice. Glucose tolerance tests showed hyperinsulinemia and hyperglycemia, indicative of insulin insensitivity in the miR-181c/d-/- mice. miR-181c/d-/- mice fed the HF diet had higher serum and liver triglyceride levels than did WT mice fed the same diet. qPCR data showed that several genes regulated by isocitrate dehydrogenase 1 (IDH1) were more upregulated in miR-181c/d-/- liver than in WT liver. Furthermore, miR-181c delivered in vivo via adeno-associated virus attenuated the lipogenesis by downregulating these same lipid synthesis genes in the liver. In hepatocytes, miR-181c regulates lipid biosynthesis by targeting IDH1. Taken together, the data indicate that overexpression of miR-181c can be beneficial for various lipid metabolism disorders. |
| format | Article |
| id | doaj-art-644d39865bfc4278afd2f14822ff6cdf |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-644d39865bfc4278afd2f14822ff6cdf2025-08-20T02:46:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011612e025697310.1371/journal.pone.0256973Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver.Kei AkiyoshiGretha J BoersmaMiranda D JohnsonFernanda Carrizo VelasquezBrittany Dunkerly-EyringShannon O'BrienAtsushi YamaguchiCharles SteenbergenKellie L K TamashiroSamarjit DasWe recently identified a nuclear-encoded miRNA (miR-181c) in cardiomyocytes that can translocate into mitochondria to regulate mitochondrial gene mt-COX1 and influence obesity-induced cardiac dysfunction through the mitochondrial pathway. Because liver plays a pivotal role during obesity, we hypothesized that miR-181c might contribute to the pathophysiological complications associated with obesity. Therefore, we used miR-181c/d-/- mice to study the role of miR-181c in hepatocyte lipogenesis during diet-induced obesity. The mice were fed a high-fat (HF) diet for 26 weeks, during which indirect calorimetric measurements were made. Quantitative PCR (qPCR) was used to examine the expression of genes involved in lipid synthesis. We found that miR-181c/d-/- mice were not protected against all metabolic consequences of HF exposure. After 26 weeks, the miR-181c/d-/- mice had a significantly higher body fat percentage than did wild-type (WT) mice. Glucose tolerance tests showed hyperinsulinemia and hyperglycemia, indicative of insulin insensitivity in the miR-181c/d-/- mice. miR-181c/d-/- mice fed the HF diet had higher serum and liver triglyceride levels than did WT mice fed the same diet. qPCR data showed that several genes regulated by isocitrate dehydrogenase 1 (IDH1) were more upregulated in miR-181c/d-/- liver than in WT liver. Furthermore, miR-181c delivered in vivo via adeno-associated virus attenuated the lipogenesis by downregulating these same lipid synthesis genes in the liver. In hepatocytes, miR-181c regulates lipid biosynthesis by targeting IDH1. Taken together, the data indicate that overexpression of miR-181c can be beneficial for various lipid metabolism disorders.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0256973&type=printable |
| spellingShingle | Kei Akiyoshi Gretha J Boersma Miranda D Johnson Fernanda Carrizo Velasquez Brittany Dunkerly-Eyring Shannon O'Brien Atsushi Yamaguchi Charles Steenbergen Kellie L K Tamashiro Samarjit Das Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. PLoS ONE |
| title | Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. |
| title_full | Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. |
| title_fullStr | Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. |
| title_full_unstemmed | Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. |
| title_short | Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver. |
| title_sort | role of mir 181c in diet induced obesity through regulation of lipid synthesis in liver |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0256973&type=printable |
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