Zanthoxylum piperitum activates thermogenic gene expression and beige adipogenesis in white adipose tissues of mice

Abstract

Metabolic syndrome increases the risk of cardiovascular disease, stroke, and diabetes mellitus. Because treatment of obesity is necessary to prevent multiple organ dysfunctions associated with metabolic syndrome, tolerable anti‐obesity drugs must be developed. In this study, we focused on Zanthoxylum piperitum (ZP), a uniquely flavored spice that confers a tingling sensation. We examined the effects of ZP on obesity and glucose–lipid metabolism in mice fed a standard diet (STD) or high‐fat diet (HFD) with or without ZP. Notably, body weight and fat mass markedly decreased, and glucose–lipid metabolism improved, in STD‐fed mice treated with ZP. Moreover, thermogenic gene expression was elevated in inguinal white adipose tissue (iWAT) from STD‐fed mice treated with 3% ZP. Immunohistochemistry of iWAT revealed uncoupling protein‐1 (UCP‐1)–positive multilocular adipocytes, suggesting induction of the beige adipogenesis. In conclusion, ZP administered in the diet decreases weight and fat mass, concomitant with induction of beige adipogenesis. These findings imply that identification of the components of ZP that exert anti‐obesity effects could facilitate development of novel anti‐obesity drugs originating from a natural food.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant Number JP25504010 (to HI), JP16K12728 (to HI), Grants‐in‐Aid from the Consortium of Higher Education Institution in Wakayama (2012&2016 to HI, 2014&2015 to KT), Research and Development Support Project for Pioneering Industrial Technology by Wakayama Prefectural Government (to NG), and a Grant‐in‐Aid from the Regional Innovation Strategy Support Program 2011–2016 (to KT).Visceral and subcutaneous fat mass were quantified by small‐animal CTFigure 1H&E staining and immunohistochemistry showed UCP‐1 positive multilocular adipocytes in iWAT from STD+3%ZP miceFigure 2