The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium

Abstract

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.

Keywords: adipose tissue; inflammation; microbiota; myocardiocytes; obesity.

Figure 1

Sick adipose tissue microenvironment and its interactions. Hypertrophic adipocytes and immune cells infiltration characterize the adipose tissue of obese individuals in response to a hypoxic environment as a signal for cell death and inflammation. This phenomenon leads to proteomic dysregulation and deflective peripheral signals promoting metabolic alterations in other tissues like muscle cells, particularly the myocardiocytes. In addition, obesogenic habits in overweighed people cause changes in the intestinal microbiota triggering adipose tissue chronic inflammation and cellular senescence. UCP2, uncoupling protein 2; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1α; PPARγ, peroxisome proliferator-activated receptor gamma; VEGF-A, vascular endothelial growth factor A; MMP, metalloproteinases; HIF1α, hypoxia-inducible factor 1α; LPS, lipopolysaccharides; SCFA, short-chain fatty acids; CB1, cannabinoid receptor 1; ECM, extracellular matrix.

Figure 2

Heart and Adipose Tissue Crosstalk: Key Messengers. Cardiokines: stimuli such as cardiac ischemia, reperfusion, oxidative and hemodynamic stress stimulate the production of cardiokines, which signaling in an endocrine and paracrine mechanism to the adipose tissue promoting weight loss by increasing thermogenesis and both the release and oxidation of fatty acids. Adipose tissue dysfunction is a stimulus for miRNAs release, which travel through the bloodstream to the myocardial tissue inside exosomes, exerting cardioprotective against myocardial infarction, coronary artery disease and atrial fibrillation. On the other hand, obesity, IR and cardiovascular diseases decrease BCAAs oxidation in adipose tissue, which decreases autophagy with heart hypertrophy and, finally, the alteration of the bioenergetic homeostasis of the heart. FA, Fatty Acids; AT, Adipose Tissue; CV, Cardiovascular; IR, Insulin resistance.