Role of Adiponectin in Cardiovascular Diseases Related to Glucose and Lipid Metabolism Disorders

Abstract

Lifestyle changes have led to increased incidence of cardiovascular disease (CVD); therefore, potential targets against CVD should be explored to mitigate its risks. Adiponectin (APN), an adipokine secreted by adipose tissue, has numerous beneficial effects against CVD related to glucose and lipid metabolism disorders, including regulation of glucose and lipid metabolism, increasing insulin sensitivity, reduction of oxidative stress and inflammation, protection of myocardial cells, and improvement in endothelial cell function. These effects demonstrate the anti-atherosclerotic and antihypertensive properties of APN, which could aid in improving myocardial hypertrophy, and reducing myocardial ischemia/reperfusion (MI/R) injury and myocardial infarction. APN can also be used for diagnosing and predicting heart failure. This review summarizes and discusses the role of APN in the treatment of CVD related to glucose and lipid metabolism disorders, and explores future APN research directions and clinical application prospects. Future studies should elucidate the signaling pathway network of APN cardiovascular protective effects, which will facilitate clinical trials targeting APN for CVD treatment in a clinical setting.

Keywords: adiponectin; atherosclerosis; cardiac hypertrophy; glucose and lipid metabolism; hypertension; myocardial infarction; myocardial ischemia/reperfusion injury.

Figure 1

(A) Domain structure of human adiponectin (APN). APN monomer is composed of a carboxyl (COOH) terminal globular domain (a), a collagen-like domain (b), a variable region, and (c) an amino (NH2) terminal signal peptide (d) [15] (B) APN structure. (B) a–d is the same as (A) a–d. Three APN monomers are connected to form a trimer (low molecular weight [LMW]), two trimers are connected to form a hexamer (medium molecular weight [MMW]), and 4–6 trimers form multimers (high molecular weight [HMW]) [14,18].

Figure 2

Schematic representation of the intracellular signaling pathways involving adiponectin (APN). APN binds to its receptors AdipoR1 and AdipoR2 and interacts with APPL1, thereby activating various signaling pathways, including AMPK, PPAR-α, and Akt pathways. Activation of these pathways leads to cellular responses, including glucose uptake stimulation, fatty acid oxidation, increased insulin sensitivity, and mitochondrial biogenesis, maintenance of cardiovascular homeostasis, reduction in inflammation, cardiac hypertrophy, and oxidative stress. Black arrows indicate activation, and flat lines indicate inhibition. Abbreviations: ACC, acetyl-CoA carboxylase; AdipoR1, adiponectin receptor 1; AdipoR2, adiponectin receptor 2; AMPK, 5′-adenosine monophosphate-activated protein kinase; Akt, protein kinase B; APPL1, adaptor protein containing pleckstrin homology domain; eNOS, endothelial nitric oxide lyase; ERK, extracellular regulated protein kinase; mTOR, mechanistic target of rapamycin; NF-κB, nuclear factor-κB; NO, nitric oxide; p38 MAPK, mitogen-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PPAR-α, peroxisome proliferator-activated receptor-α; SIRT1, silent information regulator 1; TNF-α, tumor necrosis factor-α.

Figure 3

Schematic representation of the role of adiponectin (APN) in glucose and lipid metabolism. Red dots indicate APN, red arrows indicate facilitation, and blue arrows indicate inhibition. Abbreviations: FFA, free fatty acid.

Figure 4

Schematic representation of the role of adiponectin (APN) in cardiovascular diseases related to glucose and lipid metabolism disorders. Red dots indicate APN, red arrows indicate promotion or increase, blue arrows indicate inhibition or decrease, and flat black lines indicate inhibition. Abbreviations: HDL, high-density lipoprotein; HF, heart failure; MI-R, myocardial ischemia/reperfusion; NO, nitric oxide; ROS, reactive oxygen species.