Physiological role of adiponectin in different tissues: a review (original) (raw)

Physiological Roles and Associated Disorders of Adiponectin

Asian Journal of Pharmaceutical and Clinical Research, 2016

ABSTRACTAmong the adipokines, adiponectin is the first one to be described just over a decade ago. It is produced exclusively by adipose tissue and circulatesin high concentration in human plasma accounting for 0.01% of proteins in plasma, almost thousand times higher than that of leptin. The normalcirculating level of adiponectin ranges from 2 to 30 µg/ml. It is now observed that besides adipose tissue, adiponectin can also be produced byseveral other tissues such as hepatocytes, cardiomyocytes, and placenta. Adiponectin executes its action via autocrine as well as and paracrine effects.Researchers working in this area have revealed that adiponectin has insulin-sensitizing, anti-inflammatory and cardioprotective effects. Our reviewfocuses on adiponectin, its mode of action on different peripheral tissues such as skeletal muscles, heart, liver, brain and its the correlative accountin various diseases.Keywords: Adiponectin, Obesity, Type 2 diabetes, Inflammation, Malignancies, Cardio...

Adiponectin and its Role in Cardiovascular Diseases

Cardiovascular & Hematological Disorders-Drug Targets, 2008

Studies performed during the last decade indicate that adipose tissue is not only a site of triglyceride storage but also an active endocrine organ which secretes many biologically active mediators referred to as "adipokines". In contrast to many adipokines which are overproduced in obese individuals and exert deleterious effects on insulin sensitivity, lipoprotein metabolism and cardiovascular system, such as leptin, tumor necrosis factor-, plasminogen activator inhibitor-1, resistin, etc., adiponectin seems to be a unique adipokine which is produced in lower amounts in obese than in lean subjects and possesses predominantly beneficial activities, i.e. increases insulin sensitivity, stimulates fatty acid oxidation, inhibits inflammatory reaction and induces endothelium-dependent nitric oxide-mediated vasorelaxation. Adiponectin binds two receptors, AdipoR1 and AdipoR2. Adiponectin knockout mice exhibit various manifestations of the metabolic syndrome such as insulin resistance, glucose intolerance, hyperlipidemia, impaired endothelium-dependent vasorelaxation and hypertension, as well as augmented neointima formation after vascular injury. Clinical studies indicate that plasma adiponectin concentration is lower in patients with essential hypertension and ischemic heart disease. Raising endogenous adiponectin level or increasing the sensitivity to this hormone may be a promising therapeutic strategy for patients with metabolic and cardiovascular diseases. Among currently used drugs, thiazolidinediones (peroxisome proliferator activated receptor agonists) are most effective in elevating adiponectin level.

Adiponectin: Characterization, Metabolic and Cardiovascular Action

International Journal of Cardiovascular Sciences, 2015

In the last two decades, the understanding of adipose tissue biology underwent revolutionary changes, from a major energy storage site to an important endocrine organ responsible for the production and secretion of proteins, peptides and non-bioactive peptides. Among the proteins secreted by adipocytes, adiponectin (APN) is the most abundant, with important physiological actions in the cardiovascular and endocrine system, involving the sensitization of insulin action and regulation of body energy metabolism, including the heart. This review aims to describe the action of APN on the cardiovascular system. It includes original manuscripts with humans or animals. The databases PubMed and Medline, from years 1994 to 2013, were searched. Case reports, pilot studies or review studies have not been included. The health science descriptors and MeSH specific for Medline were used as keywords. The following cross searches were carried out: Adiponectin AND Obesity, Adiponectin AND Metabolism and Adiponectin AND Cardiovascular Disease. We found 303 manuscripts, excluded 204 and selected 31 manuscripts that were included this study. In the general context of this review, APN presents anti-inflammatory and ateroprotector effects in the vascular tissue and an insulin sensitizing action in tissues involved in glucose and lipid metabolism. It is thus considered an important biomarker for the development of cardiovascular diseases.

Adiponectin - a key adipokine in the metabolic syndrome

Diabetes, Obesity and Metabolism, 2006

Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphateactivated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the highmolecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-a (TNF-a) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-a effects). Thus, adiponectin may be the common mechanism by which TNF-a promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor a ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.

Tissue-specific role and associated downstream signaling pathways of adiponectin

Cell & Bioscience

According to the World Health Organization, metabolic syndrome (MetS) can be defined as a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. The incidence of MetS keeps rising, as at least 35% of the USA population suffers from MetS. One of the worst comorbidities of metabolic syndrome are cardiovascular diseases that significantly amplifies the mortality associated with this syndrome. There is an urgent need to understand the pathophysiology of MetS to find novel diagnosis, treatment and management to mitigate the MetS and associated complications. Altered circulatory adiponectin levels have been implicated in MetS. Adiponectin has numerous biologic functions including antioxidative, anti-nitrative, anti-inflammatory, and cardioprotective effects. Being a pleiotropic hormone of multiple tissues, tissue-specific key signaling pathways of adiponectin will help finding specific target/s to blunt the pathophysiology of metab...

Adiponectin: an adipokine with protective features against metabolic syndrome

Iranian journal of basic medical sciences, 2015

Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases.

Adiponectin: Regulation of its production and role in human diseases

Adiponectin is a white and brown adipose tissue hormone, also known as gelatin-binding protein-28 (GbP28), AdipoQ, adipocyte complement-related protein (AcrP30), or apM1. Adiponectin circulates in the bloodstream in trimeric, hexameric, and high-molecular-mass species, while different forms of adiponectin have been found to play distinct roles in the balance of energy homoeostasis. Adiponectin is an insulin sensitizing hormone that exerts its action through its receptors Adipor1, Adipor2, and t-cadherin. Adipor1 is expressed abundantly in muscle, whereas Adipor2 is predominantly expressed in the liver. Adiponectin is inversely proportional to obesity, diabetes, and other insulin-resistant states. In this review we present the current findings regarding the regulation of its production and several new findings pertaining to its biological effects. Indeed, adiponectin enhances AMPK and the PPARα pathway in the liver and skeletal muscle. Adiponectin increases fatty acids oxidation, which lowers circulating free fatty acids and prevents insulin resistance. Adiponectin has been reported to exert an antiatherosclerotic effect. It inhibits macrophage activation and foam cell accumulation while it also augments endothelial nitrous oxide production and protects the vasculature by reducing platelet aggregation and vasodilation. Apart from causing metabolic dysfunction, adiponectin deficiency may also contribute to coronary heart disease, steatohepatitis, insulin resistance, nonalcoholic fatty liver disease, and a wide array of cancers. In this study, we present ample evidence that adiponectin mediates multiple molecular pathways. We therefore support the concept that it shows distinct potential for being of therapeutic value in the treatment of obesity related diseases, ranging from metabolic syndrome to malignancies.

Adiponectin: regulation of its production and its role in human diseases

Hormones (Athens, Greece)

Adiponectin is a white and brown adipose tissue hormone, also known as gelatin-binding protein-28 (GBP28), AdipoQ, adipocyte complement-related protein (ACRP30), or apM1. Adiponectin circulates in the bloodstream in trimeric, hexameric, and high-molecular-mass species, while different forms of adiponectin have been found to play distinct roles in the balance of energy homoeostasis. Adiponectin is an insulin sensitizing hormone that exerts its action through its receptors AdipoR1, AdipoR2, and T-cadherin. AdipoR1 is expressed abundantly in muscle, whereas AdipoR2 is predominantly expressed in the liver. Adiponectin is inversely proportional to obesity, diabetes, and other insulin-resistant states. In this review we present the current findings regarding the regulation of its production and several new findings pertaining to its biological effects. Adiponectin enhances AMPK and the PPARα pathway in the liver and skeletal muscle. Adiponectin increases fatty acids oxidation, which lower...