Abstract
Harmine is a natural compound possessing insulin-sensitizing effect in db/db diabetic mice. However its effect on adipose tissue browning is unknown. Here we reveal that harmine antagonizes high fat diet-induced adiposity. 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 expression 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-mediated ERK activation. CHD4 directly binds the proximal promoter region of Ucp1, which is displaced upon treatment of harmine, thereby serving as a negative modulator of Ucp1. Thus, here we reveal a new application of harmine in combating obesity via this off-target effect in adipocytes.
Highlights
Obesity, an independent risk factor for diseases ranging from metabolic syndrome to cancer, is becoming epidemic in both developing and developed countries
To explore the function of harmine in metabolic diseases, 8-week-old C57BL/6J mice were fed with high fat diet and treated with daily saline or harmine (50 mg/kg) for 8 weeks
In the current study we found that anti-tumor, anti-depressive, and anti-βcell death compound harmine, is a potent agent to promote the thermogenesis of adipocytes and prevent diet-induced obesity
Summary
An independent risk factor for diseases ranging from metabolic syndrome to cancer, is becoming epidemic in both developing and developed countries. A third type of adipocytes—beige or brite (brown in white) adipocytes—has been identified in both human and animal models[3]. These UCP1-positive, multilocular brown-like cells are scattered in white adipose tissues and readily induced upon certain stimuli. Harmine is a naturally occurring harmala alkaloid present in a number of plants and a major component of the psychoactive mixture ayahuasca. Tyrosine-regulated kinase-1a (DYRK1A), monoamine oxidase-A (MAO-A), and CDC-like kinases[7] It has both antitumor and antidepressive functions and protects against type 1 and type 2 diabetes by distinct mechanisms[8,9]. The effect of harmine and its mechanisms of action are yet to be fully elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
