Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Institut de Biomedicina de la UB University of Barcelona, Diagonal 643, E-08028 Barcelona, Spain.
Curr Mol Pharmacol. 2009 Jan;2(1):46-55. doi: 10.2174/1874467210902010046.
Metabolic syndrome is defined as the clustering of multiple metabolic abnormalities, including abdominal obesity, dyslipidemia (high serum triglycerides and low serum HDL-cholesterol levels), glucose intolerance and hypertension. The pathophysiology underlying metabolic syndrome involves a complex interaction of crucial factors, but two of these, insulin resistance and obesity (especially visceral obesity), play a major role. The nuclear receptors Peroxisome Proliferator-Activated Receptors (PPAR)alpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively. Evidence is now emerging that the PPARbeta/delta; isotype is a potential pharmacological target for the treatment of disorders associated with metabolic syndrome. PPARbeta/delta; activation increases lipid catabolism in skeletal muscle, heart and adipose tissue and improves the serum lipid profile and insulin sensitivity in several animal models. In addition, PPARbeta/delta; ligands prevent weight gain and suppress macrophage-derived inflammation. These data are promising and indicate that PPARbeta/delta; ligands may become a therapeutic option for the treatment of metabolic syndrome. However, clinical trials in humans assessing the efficacy and safety of these drugs should confirm these promising perspectives in the treatment of the metabolic syndrome.
代谢综合征定义为多种代谢异常的聚集，包括腹部肥胖、血脂异常（血清甘油三酯升高和高密度脂蛋白胆固醇水平降低）、葡萄糖耐量异常和高血压。代谢综合征的病理生理学涉及关键因素的复杂相互作用，但其中两个因素，胰岛素抵抗和肥胖（尤其是内脏肥胖），起着主要作用。过氧化物酶体增殖物激活受体（PPAR）alpha 和 PPARgamma 是治疗高甘油三酯血症和胰岛素抵抗的治疗靶点。现在有证据表明，PPARbeta/delta; 同工型是治疗与代谢综合征相关疾病的潜在药理学靶点。PPARbeta/delta; 激活增加骨骼肌、心脏和脂肪组织中的脂质分解代谢，并改善几种动物模型中的血清脂质谱和胰岛素敏感性。此外，PPARbeta/delta; 配体可预防体重增加并抑制巨噬细胞衍生的炎症。这些数据很有希望，表明 PPARbeta/delta; 配体可能成为治疗代谢综合征的一种治疗选择。然而，评估这些药物在人类中的疗效和安全性的临床试验应该在治疗代谢综合征方面证实这些有希望的观点。
