Heart over mind: metabolic control of white adipose tissue and liver

Abstract

Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

Figure 1. Metabolic communications between the heart and other tissues

More than 16 proteins secreted from the heart have thus far been identified as cardiokines. Some of these act on other tissues to regulate metabolism in an endocrine manner. (A) Upregulation of MED13 in the heart enhances lipid utilization in white adipose tissue (WAT) and liver via unidentified circulating factors but decreases lipid utilization in the heart, thereby increasing systemic energy expenditure and leading to leanness (Baskin et al, 2014). (B) Metabolic derangement in a primary genetic heart disease, such as familial hypertrophic cardiomyopathy (HCM), adversely impacts liver metabolism (Magida & Leinwand, 2014). (C) Natriuretic peptides enhance lipolysis, lipid mobilization, and thermogenesis in adipocytes, in addition to natriuresis, diuresis, and vasodilation (Rashed et al, ; Sengenes et al, ; Bordicchia et al, 2012). (D) Secretion of myostatin (and probably other cardiokines, such as activin A) from the heart is increased in heart failure (HF) and accounts for muscle wasting (Shimano et al, 2012). Myostatin secreted from the skeletal muscle regulates lipid metabolism in adipose tissue (Lee, 2004). (E) Upregulation of MED13 in the heart and muscle increases the secretion of Wingless (Wnt), which enhances lipid metabolism in adipocytes in Drosophila (Lee et al, 2014). miR-208a, microRNA-208a; MED13, Mediator complex subunit 13; ANF, atrial natriuretic factor; BNP, B-type natriuretic peptide; NPRA, natriuretic peptide receptor A; PKG, cGMP-dependent protein kinase.