MED13‐dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver

EMBO Molecular Medicine

Kedryn K Baskin²  Chad E Grueter³  Christine M Kusminski⁵  William L Holland⁵  Angie L Bookout²  Santosh Satapati⁴  Y Megan Kong²  Shawn C Burgess⁴  Craig R Malloy⁴  Philipp E Scherer⁵  Christopher B Newgard¹  Rhonda Bassel-Duby² 

[1] Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC, USA;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;Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

关键词: energy homeostasis;    mediator complex;    metabolic flexibility;    metabolic gene expression;    metabolism;   

DOI  :  10.15252/emmm.201404218

来源: Wiley

【 摘 要 】

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.

Synopsis

Cardiac MED13 enhances the use by the heart and the body of fuel resources available after or between meals. The heart thereby regulates systemic energy expenditure via circulating factors to promote enhanced metabolism and leanness.

• Cardiac overexpression of MED13 increases lipid metabolism in adipose tissue and liver.
• Enhanced metabolism in MED13cTg mice is not pathological, as MED13cTg mice metabolically adapt to fasting.
• Leanness is regulated by circulating factors in MED13cTg mice.
• Metabolic rates of wild-type mice are increased by systemic delivery of “lean factors”.

【 授权许可】

CC BY   
© 2014 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.