Table 1.
Adipocytokines involved in the pathogenesis of obesity and HF.
| Adipocytokine | Primary source of synthesis in human | Main biological function | Changes in obesity/type 2 DM (T2DM) | Role in HF | References |
|---|---|---|---|---|---|
| Adiponectin | Adipocytes | Regulation of energy homeostasis, glucose and lipid metabolism | ↓ Circulating levels and ↑ adiponectin-1 receptors depending on presentation of conventional CV risk factors | ↑ Levels are predictor of all-cause, CV, HF-related mortality, adverse cardiac remodeling, functional activity, skeletal muscle wasting, and metabolic disorders in HF | (87–98) |
| Leptin | Adipocytes | Body weight, feeding behavior, and energetic metabolism | ↑ Levels among AO and T2DM patients | ↓ Circulating levels predict HF severity, cardiac hypertrophy, pump dysfunction, cardiac and kidney fibrosis | (99–115) |
| Resistin | Macrophages | Sensitivity to insulin and FFA oxidation | ↑ Levels are associated with IR, and oxidative stress and inflammation | ↑ levels correlate with the severity of HF and predict HF outcomes | (20, 116–130) |
| Visfatin | Adipocytes, macrophages | Energy homeostasis, anti-inflammatory effect | ↑ Levels in serum correlate with IR, BMI | ↑ levels in HFpEF, ↓ levels in HFrEF | (131–142) |
| Omentin | Adipocytes, macrophages | Regulation of adipocyte differentiation, maturation, energy metabolism, immune response, inflammation, and IR | ↑ Levels in serum, ↓ levels in vascular endothelium | Predictor of hospital readmission and mortality in HF patients | (138, 143, 144, 144–151) |
| Zinc-α2-glycoprotein | Adipocytes | Promoting lipid metabolism, glucose utilization, and insulin sensitivity | ↑ Levels in serum, which correlates with omentin-1 | Predictor of early diastolic filling abnormality and LV hypertrophy | (152–161) |
| Lipocalin 2 | Adipocytes, macrophages | Regulation of inflammation and fibrosis | ↑ Serum levels in connection with IR, hs-CRP | ↑ TNF-α secretion from adipocytes, enhancing inflammation and IR | (162–166) |
| ANGPTL2 | Adipocytes | Regulation of insulin sensitivity | ↑ Serum levels and expression in WAT | Microvascular inflammation, accelerating atherosclerosis | (167, 168) |
| Secreted frizzled-related protein 5 | Adipocytes | Regulation of growth, proliferation, ECM remodeling, | ↓ Proinflammatory WNT signaling | Skeletal muscle waist and adverse cardiac remodeling | (169–171) |
| Glypican-4 | Adipocytes | Regulation of insulin sensitivity | ↑ Serum levels and expression in WAT | ↑ Serum levels and ↑ expression in cardiac tissues, WAT, vasculature correlates with IR and BMI | (172–179) |
| Retinol-binding protein-4 | Adipocytes, macrophages, hepatocytes | Regulation of insulin sensitivity | ↑ Serum levels in connection with IR | Predictor of T2DM and IR in patients with established HF | (180–183) |
| TNF-α | VSMCs, adipocytes, APCs | ↑ Local and systemic inflammation, ↓ insulin signaling | ↑ Serum levels in connection with IR and systemic inflammation | Predictor of HF-related clinical outcomes | (184–193) |
| IL-6 | Adipocytes, APCs, SVFCs, VSMCs, hepatocytes | ↑ Inflammation, signal transductor of TNF-α | ↑ Serum levels in connection with IR and systemic inflammation | Predictor of mortality | (191, 192) |
IR, insulin resistance; APCs, antigen-presenting cells; ANGPTL2, angiopoietin-like protein 2; SVFCs, stromal vascular fraction cells; VSMCs, vascular smooth muscle cells; FFA, free fatty acids; hs-CRP, high-sensitivity C-reactive protein; ECM, extracellular matrix, ↑, increase; ↓, decrease.