title: The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin.
abstract: Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Md Murad
authors.initials: MM
authors.lastname: Hossain
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Abdul
authors.initials: A
authors.lastname: Mukheem
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Clinical Investigative Centre, Faculty of Medicine, University Malaya Medical Center, Kuala Lumpur, Malaysia; Deputy Director, University Malay Hospital, Kuala Lumpur, Malaysia. Electronic address: tkzrea@um.edu.my.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D056128:Obesity, Abdominal / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D007004:Hypoglycemic Agents; D047495:PPAR gamma
keywords: Adiponectin; Adiponectin receptor agonists; Adiponectin up-regulation; Hypoadiponectinemia; PPARγ agonists