Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction

Abstract

Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.

The Important Role of Adiponectin and Orexin-A, Two Key Proteins Improving Healthy Status: Focus on Physical Activity

“…Adiponectin concentrations are strongly reduced in obesity; lower Adiponectin levels in obese patients are related to several deleterious metabolic changes (Nigro et al, 2014). Adiponectin levels increase with weight loss and improved insulin sensitivity (Shehzad et al, 2012;Nigro et al, 2014;Achari and Jain, 2017;Polito et al, 2018).…”

“…It has also been proved in obese adults that weight loss induced by diet is associated with an improvement in Adiponectin levels. On the contrary, the beneficial effects of physical exercise is associated with insulin sensitivity associated with an increase in plasma Adiponectin concentrations, even if this concept has not been completely clarified (Achari and Jain, 2017). Recent studies in lean subjects have provided inconsistent evidence, reporting both unchanged and increased Adiponectin levels after exercise.…”

Nucleus‐localized adiponectin is survival gatekeeper through miR‐214‐mediated AIFM2 regulation

“…Plasma APN/Apn has pleiotropic functions in many tissues and conditions. APN/Apn suppresses hepatic gluconeogenesis, promotes insulin sensitization and improves whole-body energy homeostasis (Achari & Jain, 2017).…”

Phytopharmacological Strategies in the Management of Type 2 Diabetes Mellitus

“…Adiponectin (Acrp30, AdipoQ, GBP-28, or apM1) is an endocrine factor, mainly secreted by the adipose tissue, but also by skeletal and cardiac myocytes and endothelial cells, with direct actions in the liver, skeletal muscle, and vasculature [19]. It exists in the circulation as varying molecular weight forms produced by multimerization, where the high-molecular weight complexes have apparent predominant action on metabolic tissues [19]. Adiponectin administration in human and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects with possible decreases of body weight [19].…”

“…It exists in the circulation as varying molecular weight forms produced by multimerization, where the high-molecular weight complexes have apparent predominant action on metabolic tissues [19]. Adiponectin administration in human and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects with possible decreases of body weight [19]. In fact, low plasma adiponectin concentrations are associated with obesity and T2DM regardless of ethnic groups, where hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than the degree of adiposity and glucose intolerance [20].…”