MED13cTg heart ventricles and epididymal fat

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 over-expression 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 and metabolite levels in heart and liver 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. n=3 for each genotype and organ心脏需要持续的能量供给，但自身储能能力极其有限，因此依赖外源性代谢来源。我们前期研究证实，小鼠心脏中的MED13可调控全身能量稳态。本研究旨在明确响应心脏MED13信号的心外组织。实验结果显示，在转基因小鼠中过表达心脏MED13（即MED13cTg小鼠）可使其呈现瘦体型表型，该表型与白色脂肪组织（white adipose tissue, WAT）及肝脏内脂质摄取增加、β氧化增强以及线粒体含量提升密切相关。心脏MED13的表达会降低心脏与肝脏内的代谢基因表达水平及代谢物含量，却可上调白色脂肪组织中的相关指标。尽管MED13cTg小鼠在进食状态下能量消耗增加，但它们仍可在禁食状态下实现代谢适应。此外，MED13cTg小鼠的心脏能够氧化现成可用的燃料，使其在进食状态下代谢效率更高。联体共生实验中，将野生型小鼠与MED13cTg小鼠的循环系统相连，结果表明MED13cTg小鼠体内的循环因子可促进代谢增强与瘦体型表型。上述研究结果证实，MED13可在心脏内发挥作用，促进心外能量储存组织的全身能量消耗，同时揭示了心脏与其他组织间一种尚未被探索的代谢通讯系统。每组基因型与器官的样本量均为3。