Mechanisms linking adipose tissue inflammation to cardiac hypertrophy and fibrosis

Abstract

Adipose tissue is classically recognized as the primary site of lipid storage, but in recent years has garnered appreciation for its broad role as an endocrine organ comprising multiple cell types whose collective secretome, termed as adipokines, is highly interdependent on metabolic homeostasis and inflammatory state. Anatomical location (e.g. visceral, subcutaneous, epicardial etc) and cellular composition of adipose tissue (e.g. white, beige, and brown adipocytes, macrophages etc.) also plays a critical role in determining its response to metabolic state, the resulting secretome, and its potential impact on remote tissues. Compared with other tissues, the heart has an extremely high and constant demand for energy generation, of which most is derived from oxidation of fatty acids. Availability of this fatty acid fuel source is dependent on adipose tissue, but evidence is mounting that adipose tissue plays a much broader role in cardiovascular physiology. In this review, we discuss the impact of the brown, subcutaneous, and visceral white, perivascular (PVAT), and epicardial adipose tissue (EAT) secretome on the development and progression of cardiovascular disease (CVD), with a particular focus on cardiac hypertrophy and fibrosis.

Keywords: adipokines; brown adipose tissue; cardiac fibrosis; cardiac hypertrophy; cardiovascular disease; obesity.

Figure 1.. Adipose-mediated paracrine signaling effects on the heart

WAT (yellow color), comprising PVAT, EAT, visceral, subcutaneous, and gonadal, is composed of droplet-rich and mitochondrial poor white adipocytes. BAT (brown color), comprising cervical, supraclavicular, auxillary, paravertebral, and suprarenal, is composed of multilocular and mitochondrial rich brown adipocytes. WAT releases several adipokines, which can result in cardioprotection, but is often associated with increased CVD, including hypertrophied cardiomyocytes and collagen deposition (blue). BAT releases BATokines that are most often associated with promoting healthy myocardium and cardioprotection from ischemic injury.