Header

UZH-Logo

Maintenance Infos

The bromodomain inhibitor N-methyl pyrrolidone reduced fat accumulation in an ovariectomized rat model


Gjoksi, Bebeka; Ghayor, Chafik; Bhattacharya, Indranil; Zenobi-Wong, Marcy; Weber, Franz E (2016). The bromodomain inhibitor N-methyl pyrrolidone reduced fat accumulation in an ovariectomized rat model. Clinical Epigenetics, 8:42.

Abstract

BACKGROUND Weight gain is one of the consequences of estrogen deficiency and constitutes a major health problem. The present study highlights the effects of N-methyl pyrrolidone (NMP) on adipogenesis in osteoporosis induced by estrogen deficiency in an ovariectomized rat model. RESULTS Ovariectomy resulted in body weight gain, increased femoral marrow adipocytes, and hypertrophic adipocytes in white adipose tissue, distorted serum leptin, and TNF-α and PPARγ levels. Treatment with NMP normalized these parameters similar to the control group. In vitro, NMP inhibited the differentiation of 3T3-L1 pre-adipocytes and hMSCs, indicating its anti-adipogenic effect. Moreover, PPARγ was significantly reduced with NMP treatment in in vivo and in vitro experiments. NMP inhibited BRD2 and BRD4 binding in an AlphaScreen assay, with an IC50 of 3 and 4 mM, respectively. The effect of NMP was consistent with its role as a bromodomain inhibitor. CONCLUSIONS Our data indicates that NMP inhibits the adipogenic effect of estrogen deficiency at the level of PPARγ expression by BRD4 inhibition.

Abstract

BACKGROUND Weight gain is one of the consequences of estrogen deficiency and constitutes a major health problem. The present study highlights the effects of N-methyl pyrrolidone (NMP) on adipogenesis in osteoporosis induced by estrogen deficiency in an ovariectomized rat model. RESULTS Ovariectomy resulted in body weight gain, increased femoral marrow adipocytes, and hypertrophic adipocytes in white adipose tissue, distorted serum leptin, and TNF-α and PPARγ levels. Treatment with NMP normalized these parameters similar to the control group. In vitro, NMP inhibited the differentiation of 3T3-L1 pre-adipocytes and hMSCs, indicating its anti-adipogenic effect. Moreover, PPARγ was significantly reduced with NMP treatment in in vivo and in vitro experiments. NMP inhibited BRD2 and BRD4 binding in an AlphaScreen assay, with an IC50 of 3 and 4 mM, respectively. The effect of NMP was consistent with its role as a bromodomain inhibitor. CONCLUSIONS Our data indicates that NMP inhibits the adipogenic effect of estrogen deficiency at the level of PPARγ expression by BRD4 inhibition.

Statistics

Citations

Altmetrics

Downloads

9 downloads since deposited on 10 Jan 2017
9 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic for Cranio-Maxillofacial Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:10 Jan 2017 15:51
Last Modified:14 Nov 2017 22:09
Publisher:BioMed Central
ISSN:1868-7075
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13148-016-0209-2
PubMed ID:27110299

Download

Download PDF  'The bromodomain inhibitor N-methyl pyrrolidone reduced fat accumulation in an ovariectomized rat model'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 996kB
View at publisher