Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes

Abstract

Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy. Interestingly, this depot may be also related to epicardial fat accumulation through secretion of lipids, adipokines, and pro-inflammatory and oxidative factors from adipocytes. Thus, visceral adiposity and its white single-lipid-like adipocytes, are risk factors for different forms of heart disease and heart failure, mainly in higher degree obese subjects. However, under specific stimuli, some of these adipocytes can transdifferentiate to brown multi-mitochondrial-like adipocytes with anti-inflammatory and anti-apoptotic proprieties. Accordingly, in order to improve potential cardiovascular abnormalities in obese and T2DM patients, several therapeutic strategies have been addressed to modulate the visceral and epicardial fat volume and phenotypes. In addition to lifestyle modifications, specific genetic manipulations in adipose tissue and administration of PPARγ agonists or statins, have improved fat volume and phenotype, and cardiovascular failures. Furthermore, incretin stimulation reduced visceral and epicardial fat thickness whereas increased formation of brown adipocytes, alleviating insulin resistance and associated cardiovascular pathologies.

Keywords: BAT; Epicardial adipose tissue; Incretin; PPARγ; Statin; Visceral adipose tissue; WAT.

Fig. 1

VAT and EAT alterations under obesity and T2DM. In non-obese and non-T2DM subjects, WAT and BAT deposits in both VAT and EAT serve as storages and buffers for fatty acids (FA), attenuators of glycaemia and dyslipidaemia, and as controllers of vascular tension and inflammation. However, under abnormal or excessive fat accumulation, WAT and BAT depots become thicker and dysfunctional. WAT hypertrophies and it saturates, releasing FA and pro-inflammatory factors (cytokines, chemokines, RAAS) towards circulation and myocardium, leading to immune cells (IC) infiltration, myocardial steatosis and insulin resistance. BAT becomes reduced, atrophied and inactive (UCP-1 negative), losing its protective anti-glycemic/dyslipemic and anti-inflammatory effects

Fig. 2

Prospective fat-modulating interventions for cardiovascular dysfunction in obesity and T2DM. In addition to lifestyle modifications on diet and exercise, cardiovascular complications in patients with increased VAT and EAT may be treated with statins or genetic manipulations (focused on USF1, CIDE-A, PGC1a, UCP-1, PRDM-16 or miR-125b-5p) to decrease WAT thickness/pro-inflammation in EAT or increase WAT browning in VAT, respectively. More significant, PPARγ agonists could promote these effects particularly in EAT, and additionally, incretin stimulation might also induce adipocyte hyperplasia, and subsequent insulin sensitivity