Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Abstract

The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells. It acts through two main receptors: AdipoR1 and AdipoR2, forming the "Adiponectin system" which effectively exerts its cellular mechanisms and responses in target cells. It regulates various metabolic processes, while adiponectin is the adipocyte hormone known for its cardioprotective impact in clinical and experimental research. It is also a well-effector metabolic adipokine, since weight loss or diet restriction show a link with rises in adiponectin concentrations, which is accompanied with increasing insulin sensitivity, glucose, and lipids-regulation via adiponectin's antioxidant, anti-inflammatory, anti-fibrotic actions. The high adiponectin level made it an attractive player in developing therapeutical treatments for metabolic syndromes and cardiovascular disease. The elevated plasma levels of adiponectin are mostly attributed to its benefits on cardio-metabolism. In some cases, adiponectin has been paradoxically accompanied with elevated risk of cardiovascular disease, so higher adiponectin concentration is a marker of poor prediction. Thus, the adiponectin system is attractive to researchers as a biomarker of heart disease advancement and a predictor of prognosis during the term of some cardiovascular diseases and its mechanical functions in Hypertension and diabetic patients. This review highlights the physiological roles of adiponectin as an anti-inflammatory and cardioprotective hormone as well as how it plays as a biomarker and potential therapeutic tool in the cardiovascular system in adult, children, and adolescents. The adiponectin system may be seen as a rescue hormone aiding in remodeling of the cardiovascular system on both cellular and molecular levels. The paradox role of adiponectin relevant to cardiovascular mortality should be taken into consideration.

Keywords: adiponectin; cardiovascular disease; diabetes; hormone; receptor.

Figure 1

Adiponectin sources: Adiponectin is produced by adipocytes, endothelial and skeletal cells. Cardiac myocytes are also able to produce adiponectin. Its functions include antiapoptotic, anti-inflammatory, antioxidant, and anti-fibrotic effects. Adiponectin protects against CDV, controls glucose and insulin, and protects against heart, lung, and colon diseases.

Figure 2

Physiological and pathological links of adiponectin to Obesity, Cardiovascular disease (CVD), and Diabetes.

Figure 3

Paradoxical effect of adiponectin.

Figure 4

An increase in CTRP9, an adiponectin paralog, was found to increase in myocardial ischemia- reperfusion injury in plasma and fat tissue expression. When ischemic heart was treated with CTRP9, an increase in phosphorylation of AMPK led to a decrease in myocyte apoptosis.

Figure 5

Expression of adiponectin receptors in various organs‘ cells.

Figure 6

Multiple adiponectin receptor pathways in the cells.

Figure 7

Gene array analysis observation of pressure overload (PO) and duration on adiponectin knockout (AdKO) and wild-type (WT) mice of cardiac cells.