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.
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.
Life Sci. 2015 Aug 15;135:55-67. doi: 10.1016/j.lfs.2015.03.010. Epub 2015 Mar 26.
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.
低 adiponectin 血症的特征是血浆 adiponectin 水平降低，其原因可能是遗传因素，如单核苷酸多态性（SNP）和 adiponectin 基因的突变，也可能是内脏脂肪沉积/肥胖所致。有报道称，低 adiponectin 血症与血脂异常、高血压、高尿酸血症、代谢综合征、动脉粥样硬化、2 型糖尿病和各种心血管疾病有关。先前的研究强调了几种潜在的策略来上调 adiponectin 的分泌和功能，包括通过饮食疗法和运动减少内脏脂肪、外源性 adiponectin 的给药、过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂（如噻唑烷二酮类（TZDs））和配体（如 bezafibrate 和 fenofibrate）的治疗或肾素-血管紧张素系统的阻断。同样，通过使用 adiponectin 受体激动剂上调 adiponectin 受体的表达和刺激也将是治疗肥胖相关疾病的有效方法。值得注意的是，adiponectin 是一种表达丰富的生物活性蛋白，具有广泛的生物学特性，如胰岛素增敏、抗糖尿病、抗炎和抗动脉粥样硬化作用。虽然在实验研究中靶向 adiponectin 及其受体在治疗糖尿病和其他代谢相关疾病方面是有用的，但目前基于 adiponectin/adiponectin 受体的药物开发用于临床应用的还很少，并且缺乏可用的临床试验数据。这篇综述全面讨论了目前正在探索的利用 adiponectin 上调潜力的策略。此外，我们还研究了药物开发的现状及其在临床应用中的潜力。
