Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate.

Abstract

Cardiovascular disease is the leading cause of death throughout most of the industrialized world. Metabolic syndrome (MetS) and its associated pathologies are underlying factors in the etiology of cardiovascular disease, as well as a plethora of other maladies which cause excess morbidity and mortality. Adipose tissue (AT) has come to be regarded as a bona fide endocrine organ which secretes specific molecular entities constituting part of a complex web of inter-organ crosstalk that functions as a key determinant of whole-body metabolic phenotype. Brown adipose tissue (BAT) has classically been regarded as a thermogenic tissue exerting its metabolic effects primarily through its capacity to oxidize substrates decoupled from ATP resynthesis, thereby resulting in increased energy expenditure (EE) and heat production. However, in recent years, BAT has begun to receive attention as a secretory organ in its own right. The molecules secreted specifically by BAT have been termed "batokines", and currently available evidence supports the notion that batokines exert favorable metabolic effects on multiple organ systems. While maintenance of healthy body composition by conferring resistance to excessive adiposity is a rather obvious mechanism by which BAT operates via increased EE, effects on critical organs such as the heart remain unclear. This narrative review focuses on four types of batokines (FGF21, neuregulin 4, 12,13-diHOME, and BAT-derived microRNAs) for which evidence of modulation of cardiovascular function exists in the context of pathological states such as hypertension, atherosclerosis, and ischemia/reperfusion injury. Given the overwhelming burden of cardiometabolic disease, further study of the functions of BAT and its secretome is warranted and will intensify in the future.