Hattori Hiroyuki, Mori Takashi, Shibata Takahiro, Kita Masaki, Mitsunaga Tohru
Asian Satellite Campuses Institute, Nagoya University, Nagoya, 464-8601, Japan.
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Mol Nutr Food Res. 2021 Aug;65(16):e2100185. doi: 10.1002/mnfr.202100185. Epub 2021 Jun 30.
Grains of Paradise (GOP), the seeds of Aframomum melegueta, has anti-obesity effects. However, the mechanisms underlying the effects remain unclear.
This study sets up to study the anti-obesity impact and homeostatic effects of 6-paradol, a major vanilloid found in GOP, and investigates the physiological outputs and the lipometabolism-related gene in fat and liver in high-fat-induced obese mice with a comparison with structurally similar vanilloids (6-gingerol and 6-shogaol). The vanilloids are synthesized in adequate quantities for performing animal experiments and orally administered to 6-week-old male mice over 2 weeks. This study found that 6-paradol decreased body weight gain and visceral and subcutaneous fats in 2 weeks, whereas 6-gingerol and 6-shogaol have no effect. Additionally, 6-paradol suppresses the hepatic cholesterol and triglyceride and significantly decreases the gene expression related to fatty acid synthesis, lipid transportation, and adipocyte differentiation in both liver and adipose tissue. Moreover, phosphorylation of AMP-activated protein kinase (AMPK) that greatly contributes to lipometabolism is promoted by 6-gingerol but not 6-paradol.
These results suggest that 6-paradol regulates several obesity-related genes in an AMPK-independent manner. Therefore, it could be the principal active vanilloid in GOP giving it anti-obesity properties with a different mechanism.
天堂谷物（GOP），即非洲豆蔻的种子，具有抗肥胖作用。然而，其作用的潜在机制仍不清楚。
本研究旨在研究6-姜辣醇（一种在GOP中发现的主要香草酸）的抗肥胖影响和稳态效应，并研究高脂诱导肥胖小鼠脂肪和肝脏中的生理输出及脂代谢相关基因，同时与结构相似的香草酸（6-姜酚和6-姜烯酚）进行比较。这些香草酸被合成足够的量用于进行动物实验，并在2周内口服给予6周龄雄性小鼠。本研究发现，6-姜辣醇在2周内可降低体重增加以及内脏和皮下脂肪，而6-姜酚和6-姜烯酚则无此作用。此外，6-姜辣醇可抑制肝脏胆固醇和甘油三酯，并显著降低肝脏和脂肪组织中与脂肪酸合成、脂质运输及脂肪细胞分化相关的基因表达。而且，对脂代谢有很大贡献的AMP活化蛋白激酶（AMPK）的磷酸化由6-姜酚促进，而非6-姜辣醇。
这些结果表明，6-姜辣醇以不依赖AMPK的方式调节多个与肥胖相关的基因。因此，它可能是GOP中赋予其抗肥胖特性的主要活性香草酸，且作用机制不同。
