Mukherjee Jogeshwar, Baranwal Aparna, Schade Kimberly N
B140 Medical Sciences, Department of Radiological Sciences, University of California - Irvine, Irvine, CA 92697-5000, USA.
Curr Diabetes Rev. 2016;12(4):414-428. doi: 10.2174/1573399812666160517115450.
Increasing efforts are being made towards pharmacologic activation of brown adipose tissue (BAT) in animals and humans for potential use in the treatment of obesity and diabetes. We and others have reported a number of animal studies using either experimental or therapeutic drugs. There are now efforts to translate these findings to human studies. The goal of this review is to evaluate the various drugs currently being used that have the potential for BAT activation.
Drugs were classified into 4 classes based on their mechanism of action. Class 1 drugs include the use of β3 adrenoceptor agonists for BAT activation. Class 2 drugs include drugs that affect norepinephrine levels and activate BAT with the potential of reducing obesity. Class 3 includes activators of peroxisome proliferator-activated receptor-γ in pursuit of lowering blood sugar, weight loss and diabetes and finally Class 4 includes natural products and other emerging drugs with limited information on BAT activation and their effects on diabetes and weight loss.
Class 1 drugs are high BAT activators followed by Class 2 and 3. Some of these drugs have now been extended to diabetes and obesity animal models and human BAT studies. Drugs in Class 3 are used clinically for Type 2 diabetes, but the extent of BAT involvement is unclear.
Further studies on the efficacy of these drugs in diabetes and measuring their effects on BAT activation using noninvasive imaging will help in establishing a clinical role of BAT.
为了将棕色脂肪组织(BAT)的药理激活作用应用于肥胖症和糖尿病的治疗,人们在动物和人体上做出了越来越多的努力。我们和其他研究人员已经报道了多项使用实验药物或治疗药物的动物研究。目前,人们正在努力将这些研究结果转化为人体研究。本综述的目的是评估目前正在使用的具有激活BAT潜力的各类药物。
根据药物的作用机制将其分为4类。第1类药物包括使用β3肾上腺素能受体激动剂来激活BAT。第2类药物包括影响去甲肾上腺素水平并激活BAT从而有可能减轻肥胖的药物。第3类包括过氧化物酶体增殖物激活受体γ的激活剂,用于降低血糖、减轻体重和治疗糖尿病,最后第4类包括天然产物和其他新兴药物,关于它们对BAT激活及其对糖尿病和体重减轻影响的信息有限。
第1类药物是高效的BAT激活剂,其次是第2类和第3类。其中一些药物现已扩展到糖尿病和肥胖动物模型以及人体BAT研究。第3类药物临床上用于2型糖尿病,但BAT参与的程度尚不清楚。
进一步研究这些药物在糖尿病中的疗效,并使用无创成像技术测量它们对BAT激活的影响,将有助于确立BAT的临床作用。