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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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic of Cranio-Maxillofacial Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Biology
Life Sciences > Genetics
Life Sciences > Developmental Biology
Health Sciences > Genetics (clinical)
Language:English
Date:2016
Deposited On:10 Jan 2017 15:51
Last Modified:16 Oct 2024 01:37
Publisher:BioMed Central
ISSN:1868-7075
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13148-016-0209-2
PubMed ID:27110299
Project Information:
  • Funder: SNSF
  • Grant ID: 31003A_140868
  • Project Title: The potential of N-methylpyrrolidone to prevent osteoporosis and to enhance bone regeneration
  • Funder: SNSF
  • Grant ID: CR32I3_152809
  • Project Title: Osteoconductive and osteoinductive customized implants for large mandibular defects
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