TR(i)P for health Laboratory, Centre of Excellence in Functional Foods, National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab, 140603, India.
Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
Int J Obes (Lond). 2022 Jan;46(1):153-161. doi: 10.1038/s41366-021-00967-3. Epub 2021 Sep 25.
Bioactive dietary constituents activating Transient receptor potential (TRP) channels have emerged as promising candidates for the prevention of metabolic disorders.
The present study is an attempt to evaluate anti-obesity potential of a dietary TRP-based tri-agonist, combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist), and cinnamaldehyde (TRPA1 agonist) in high-fat diet (HFD)-fed mice.
Male C57BL/6 J mice divided into three groups (n = 8), were fed on normal pellet diet (NPD), or high-fat diet (HFD) (60% energy by fat) and HFD + CB (combination of capsaicin 0.4 mg/Kg, menthol 20 mg/Kg, and cinnamaldehyde 2 mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied.
Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis, and adipose tissue hypertrophy. Tri-agonist supplementation was found to induce browning of white adipose tissue and promote brown adipose tissue activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with a tri-agonist.
The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.
激活瞬时受体电位 (TRP) 通道的生物活性膳食成分已成为预防代谢紊乱的有前途的候选物。
本研究试图评估高脂肪饮食 (HFD) 喂养的小鼠中基于 TRP 的三激动剂（辣椒素 (TRPV1 激动剂)、薄荷醇 (TRPM8 激动剂) 和肉桂醛 (TRPA1 激动剂) 的亚有效剂量组合）的抗肥胖潜力。
雄性 C57BL/6J 小鼠分为三组（n = 8），分别喂食正常颗粒饮食 (NPD)、高脂肪饮食 (HFD)（脂肪提供 60% 的能量）和 HFD + CB（辣椒素 0.4mg/Kg、薄荷醇 20mg/Kg 和肉桂醛 2mg/Kg 的组合；口服）12 周。研究了三激动剂对 HFD 诱导的体重增加、WAT、BAT、肝脏和下丘脑组织的生化、组织学和基因组变化的影响。
三激动剂的给药可预防 HFD 诱导的体重增加，改善改变的形态计量学参数、葡萄糖稳态和脂肪组织肥大。发现三激动剂补充可诱导白色脂肪组织褐变并促进棕色脂肪组织激活。补充三激动剂可增强葡萄糖利用并预防肝脏脂质积累和胰岛素抵抗。
本工作提供的证据表明，基于 TRP 通道激动剂（三激动剂）的亚有效剂量组合的新方法可用于开发基于概念的功能性食品，以针对 HFD 相关的病理并发症制定治疗和预防策略。
