Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 799, Issue -, Pages 201-210Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2017.02.021
Keywords
Butein; HO-1; Nrf2; P38 MAPK; Adipose hypertrophy; Glucose intolerance
Categories
Funding
- National Research Foundation of Korea Grant - Korean Government [NRF-2012R1A1A1014527, 2014R1A1A3053867]
- National Research Foundation of Korea [2014R1A1A3053867] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2). Butein modulation of Keapl and Nrf2 as well as HO-1 upregulation was reversed by pretreatment with p38 MAPK inhibitor SB203580, indicating the involvement of p38 MAPK in butein activation of Nrf2 in adipocytes. In addition, HO-1 activation by butein led to the inhibitions of reactive oxygen species and adipocyte differentiation, as evidenced by the fact that butein repression of reactive oxygen species and adipogenesis was reversed by pretreatment with HO-1 inhibitor SnPP. Induction of HO-1 expression by butein was also demonstrated in the adipose tissue of C57BL/6 mice fed a high-fat diet administered along with butein for three weeks, and correlated with the inhibitions of adiposity and adipose tissue inflammation, which were reversed by co-administration of SnPP. Altogether, our results demonstrate that butein activates the p38 MAPK/Nrf2/H0-1 pathway to act as a potent inhibitor of adipose hypertrophy and inflammation in a diet-induced obesity model and thus has potential for suppressing obesity linked metabolic syndrome.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available