肥満と減量療法のジャーナル

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Zanthoxylum piperitum Activates Thermogenic Gene Expression and Induces Beige Adipogenesis in White Adipose Tissues of Mice

Ken Takeshima, Akio Kadowaki, Nobuki Gato, Sayo Fujita, Kunihiro Kishida, Takashi Akamizu, Hayato Ihara

Background: Zanthoxylum piperitum (ZP) is a spice that is widely used in Asia. It is uniquely flavored and creates a tingling sensation in the mouth and tongue. An anti-obesity effect from ZP has been reported, but the mechanism is not well understood.

Objective: To evaluate the effects of ZP on adiposity.

Methods: Fresh fruits of ZP were dried and its pericarp was crushed into powder. ZP-powder was orally administered to mice fed with either a standard diet (STD) or high-fat diet (HFD) for eight weeks. Food intake and body weight were measured every day. At the end of the study, organs were excised. Gene expression analysis and immunohistochemistry of white adipose tissue were performed to evaluate the effects of ZP on adiposity.

Results: ZP markedly decreased body weight and fat mass and improved glucose–lipid metabolism in STD-fed mice, but there was no significant decrease in food intake. We therefore suspected ZP-induced activation of energy expenditure in adipocytes. ZP reduced food intake of HFD-fed mice, so we hypothesized that there may be inhibition of HFD-induced hedonic eating. We also analyzed thermogenic gene expressions in inguinal white adipose tissue (iWAT) to see if ZP induced beige adipogenesis. ZP notably increased expression levels of uncoupling protein-1 (UCP- 1), peroxisome proliferator–activated receptor gamma coactivator 1-alpha (PGC1α and cell death–inducing DFFAlike effector a (Cidea) in iWAT from both STD- and HFD-fed mice. Immunohistochemistry of the iWAT revealed the presence of multilocular adipocytes that were stained with UCP-1, which suggests induction of beige adipogenesis.

Conclusion: ZP activates thermogenic gene expressions and induces beige adipogenesis in inguinal white adipose tissue of mice. Moreover, ZP was shown to inhibit hedonic eating in mice fed with a high fat diet. These effects of ZP could be utilized in complementary treatment of obesity.