Adiponectin signaling and function in insulin target tissues

Abstract

Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance.

Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice

“…8 Adiponectin exerts its biological functions by binding to its receptor to trigger the downstream signaling pathways. 9,10 Among the identified adiponectin receptors (AdipoRs), AdipoR1 and AdipoR2 have been shown to be the most physiologically important for adiponectin functions in vivo.…”

“…9 Physiologically, AdipoR1 and AdipoR2 have some common and different functions. Either of them can regulate glucose and lipid metabolism, inflammation, and oxidative stress in the liver.…”

Relationship between asymmetric dimethylarginine in umbilical cord plasma and birth weight follows a U-shaped curve

“…These findings suggest the importance of adiponectin in the regulation of body fat mass in newborn infants. A growing body of evidence suggests that adiponectin may also play a role in the development of insulin resistance [34]. Kajantie et al reported that adiponectin concentrations in fetal circulation showed a 20-fold rise between 24 week gestation [35].…”

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

“…Adiponectin -Adiponectin (Ad) is a protein hormone produced exclusively by adipose tissues with identified beneficial effects on insulin sensitivity and lipid metabolism [39]. In addition, Ad exerts multiple vasoprotective effects via its anti-inflammatory, antioxidant, antiapoptotic, antiatherogenic, vasodilatory, and antithrombotic properties on endothelial cells, monocytes, macrophages, leukocytes, platelets, and vascular smooth muscle cells [40].…”