National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India 160071; Biotechnology division, University Institute of Engineering and Technology (UIET), Panjab University, Chandigarh, India 160036.
National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India 160071.
Nutr Res. 2018 Mar;51:40-56. doi: 10.1016/j.nutres.2017.11.006. Epub 2017 Dec 5.
Despite the lipolytic and thermogenic properties of capsaicin, its putative use as a weight-lowering dietary supplement has been limited because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes. A potential alternative to capsaicin are the capsinoids, nonpungent capsaicin analogs that exhibit effects similar to capsaicin. Whereas the antiobesity properties of capsinoids have been reported, the effectiveness of FDA-approved synthetic dihydrocapsiate has not yet been investigated. In the present study, we hypothesized that dihydrocapsiate might ameliorate high-fat diet (HFD)-induced metabolic disorders in a manner similar to capsaicin and therefore can be its nonpungent alternative. To test this hypothesis, HFD-fed mice were orally administered dihydrocapsiate (2 and 10mg/kg body weight) for 12weeks. Dihydrocapsiate modestly reduced the HFD-induced weight gain and significantly prevented the associated hyperglyceridemia and hyperinsulinemia while improving glucose tolerance. Histological and gene expression analysis showed that dihydrocapsiate significantly prevented the lipid accumulation in white adipose tissue and brown adipose tissue via targeting genes involved in energy expenditure and mitochondrial biogenesis, respectively. Dihydrocapsiate corrected hepatic triglyceride concentrations and normalized expression of genes regulating hepatic lipid and glucose metabolism. Moreover, dihydrocapsiate administration significantly improved gut morphology and altered gut microbial composition, resulting in reduced host energy availability. Collectively, these results indicate that dihydrocapsiate administration improved glucose tolerance, prevented adiposity and hepatic steatosis, as well as improved HFD-induced gut alterations, positing dihydrocapsiate as a potential food ingredient for the dietary management of HFD-induced metabolic alterations.
尽管辣椒素有脂肪分解和产热作用，但由于接触粘膜时会引起烧灼感，因此其作为减肥膳食补充剂的应用受到限制。辣椒素的潜在替代品是辣椒素类似物，即无刺激性的辣椒素类似物，其具有与辣椒素相似的作用。虽然已经报道了辣椒素类似物的抗肥胖特性，但尚未研究 FDA 批准的合成二氢辣椒素的有效性。在本研究中，我们假设二氢辣椒素可能以类似于辣椒素的方式改善高脂肪饮食（HFD）引起的代谢紊乱，因此可以作为其无刺激性的替代品。为了验证这一假设，用二氢辣椒素（2 和 10mg/kg 体重）对 HFD 喂养的小鼠进行口服治疗 12 周。二氢辣椒素适度减轻了 HFD 引起的体重增加，并显著预防了相关的高甘油血症和高胰岛素血症，同时改善了葡萄糖耐量。组织学和基因表达分析表明，二氢辣椒素通过靶向分别参与能量消耗和线粒体生物发生的基因，显著预防了白色脂肪组织和棕色脂肪组织中的脂质积累。二氢辣椒素纠正了肝甘油三酯浓度，并使调节肝脂质和葡萄糖代谢的基因表达正常化。此外，二氢辣椒素给药显著改善了肠道形态并改变了肠道微生物组成，从而减少了宿主的能量供应。总之，这些结果表明，二氢辣椒素给药可改善葡萄糖耐量，预防肥胖和肝脂肪变性，并改善 HFD 引起的肠道改变，提示二氢辣椒素可作为饮食管理 HFD 诱导的代谢改变的潜在食品成分。
