MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver
Abstract The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here, we sought to define the extra‐cardiac tissue(s) that respo...
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| Format: | Article |
| Language: | English |
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Springer Nature
2014-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201404218 |
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| author | Kedryn K Baskin Chad E Grueter Christine M Kusminski William L Holland Angie L Bookout Santosh Satapati Y Megan Kong Shawn C Burgess Craig R Malloy Philipp E Scherer Christopher B Newgard Rhonda Bassel‐Duby Eric N Olson |
| author_facet | Kedryn K Baskin Chad E Grueter Christine M Kusminski William L Holland Angie L Bookout Santosh Satapati Y Megan Kong Shawn C Burgess Craig R Malloy Philipp E Scherer Christopher B Newgard Rhonda Bassel‐Duby Eric N Olson |
| author_sort | Kedryn K Baskin |
| collection | DOAJ |
| description | Abstract The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here, we sought to define the extra‐cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac overexpression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta‐oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression in the heart but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild‐type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra‐cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues. |
| format | Article |
| id | doaj-art-30c5796f91024edaa0e87fbd9613c8d6 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2014-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-30c5796f91024edaa0e87fbd9613c8d62025-08-20T04:02:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842014-11-016121610162110.15252/emmm.201404218MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liverKedryn K Baskin0Chad E Grueter1Christine M Kusminski2William L Holland3Angie L Bookout4Santosh Satapati5Y Megan Kong6Shawn C Burgess7Craig R Malloy8Philipp E Scherer9Christopher B Newgard10Rhonda Bassel‐Duby11Eric N Olson12Department of Molecular Biology, University of Texas Southwestern Medical CenterDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of MedicineTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical CenterTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical CenterDepartment of Molecular Biology, University of Texas Southwestern Medical CenterAdvanced Imaging Research Center, University of Texas Southwestern Medical CenterDepartment of Molecular Biology, University of Texas Southwestern Medical CenterAdvanced Imaging Research Center, University of Texas Southwestern Medical CenterAdvanced Imaging Research Center, University of Texas Southwestern Medical CenterTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical CenterSarah W. Stedman Nutrition and Metabolism Center, Duke UniversityDepartment of Molecular Biology, University of Texas Southwestern Medical CenterDepartment of Molecular Biology, University of Texas Southwestern Medical CenterAbstract The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here, we sought to define the extra‐cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac overexpression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta‐oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression in the heart but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild‐type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra‐cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues.https://doi.org/10.15252/emmm.201404218energy homeostasismediator complexmetabolic flexibilitymetabolic gene expressionmetabolism |
| spellingShingle | Kedryn K Baskin Chad E Grueter Christine M Kusminski William L Holland Angie L Bookout Santosh Satapati Y Megan Kong Shawn C Burgess Craig R Malloy Philipp E Scherer Christopher B Newgard Rhonda Bassel‐Duby Eric N Olson MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver EMBO Molecular Medicine energy homeostasis mediator complex metabolic flexibility metabolic gene expression metabolism |
| title | MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| title_full | MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| title_fullStr | MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| title_full_unstemmed | MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| title_short | MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| title_sort | med13 dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver |
| topic | energy homeostasis mediator complex metabolic flexibility metabolic gene expression metabolism |
| url | https://doi.org/10.15252/emmm.201404218 |
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