Baskin Kedryn K, Grueter Chad E, Kusminski Christine M, Holland William L, Bookout Angie L, Satapati Santosh, Kong Y Megan, Burgess Shawn C, Malloy Craig R, Scherer Philipp E, Newgard Christopher B, Bassel-Duby Rhonda, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
EMBO Mol Med. 2014 Dec;6(12):1610-21. doi: 10.15252/emmm.201404218.
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.
心脏需要持续的能量供应，但能量储存能力有限，因此依赖于外源性代谢来源。我们之前表明，心脏中的MED13调节小鼠的全身能量稳态。在此，我们试图确定对心脏MED13信号作出反应的心脏外组织。我们发现，转基因（MED13cTg）小鼠心脏中MED13的过表达赋予了瘦型表型，这与白色脂肪组织（WAT）和肝脏中脂质摄取增加、β-氧化和线粒体含量增加有关。MED13在心脏中的表达降低了心脏中代谢基因的表达，但增强了WAT中的代谢基因表达。尽管MED13cTg小鼠在进食状态下能量消耗增加，但它们在代谢上能适应禁食。此外，MED13cTg心脏氧化容易获得的燃料，使其在进食状态下更有效率。将野生型和MED13cTg小鼠的循环连接起来的联体实验表明，MED13cTg小鼠中的循环因子促进了新陈代谢增强和变瘦。这些发现表明，MED13在心脏内发挥作用，促进心脏外能量储存部位的全身能量消耗，并指向心脏与其他组织之间一个未被探索的代谢通讯系统。
