Poster Presentation

Harmine, a natural product capable of in situ adipocyte cell fate reprogramming

Professor Wu Donghai
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

Abstract

Harmine is a natural compound possessing insulin-sensitizing effect in db/db diabetic mice. But its effect on adipose tissue browning is unknown. Here we found that harmine antagonizes high fat diet-induced adiposity and induces the so called white adipocyte "browning" or adipocyte cell fate reprogramming. Harmine-treated mice gained less weight on a high fat diet and displayed increased energy expenditure and adipose tissue thermogenesis. In vitro, harmine potently induced the expressions of thermogenic genes in both brown and white adipocytes, which was largely abolished by inhibition of RAC1/MEK/ERK pathway. Post-transcriptional modification analysis revealed that chromodomain helicase DNA binding protein 4 (CHD4) is a potential downstream target of harmine-elicited ERK activation. CHD4 directly bound in the proximal promoter region of Ucp1, which was released upon treatment of harmine and thereby served as a negative modulator of Ucp1. Thus, here we reveal a new role of harmine in combating obesity via its off-target effect in adipocytes.