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Simvastatin downregulates adipogenesis in 3T3-l1 preadipocytes and orbital fibroblasts from graves’ ophthalmopathy patients

Shahida, B. LU ; Johnson, P. Sahlstrand LU ; Jain, R. LU ; Brorson, H. LU ; Åsman, P. LU ; Lantz, M. LU and Planck, T. LU (2019) In Endocrine Connections 8(9). p.1230-1239
Abstract

Background: Smoking is a strong risk factor for the development of Graves’ ophthalmopathy (GO). Immediate early genes (IEGs) are overexpressed in patients with active GO compared to healthy controls. The aim of this study was to study the effects of tobacco smoking and simvastatin on preadipocytes and orbital fibroblasts (OFs) in the adipogenic process. Methods: Cigarette smoke extract (CSE) was generated by a validated pump system. Mouse 3T3-L1 preadipocytes or OFs were exposed to 10% CSE with or without simvastatin. Gene expression was studied in preadipocytes and OFs exposed to CSE with or without simvastatin and compared to unexposed cells or cells treated with a differentiation cocktail. Results: In 3T3-L1 preadipocytes, Cyr61,... (More)

Background: Smoking is a strong risk factor for the development of Graves’ ophthalmopathy (GO). Immediate early genes (IEGs) are overexpressed in patients with active GO compared to healthy controls. The aim of this study was to study the effects of tobacco smoking and simvastatin on preadipocytes and orbital fibroblasts (OFs) in the adipogenic process. Methods: Cigarette smoke extract (CSE) was generated by a validated pump system. Mouse 3T3-L1 preadipocytes or OFs were exposed to 10% CSE with or without simvastatin. Gene expression was studied in preadipocytes and OFs exposed to CSE with or without simvastatin and compared to unexposed cells or cells treated with a differentiation cocktail. Results: In 3T3-L1 preadipocytes, Cyr61, Ptgs2, Egr1 and Zfp36 expression levels were two-fold higher in cells exposed to CSE than in unexposed cells. Simvastatin downregulated the expression of these genes (1.6-fold, 5.5-fold, 3.3-fold, 1.4-fold, respectively). CSE alone could not stimulate preadipocytes to differentiate. Scd1, Ppar-γ and adipogenesis were downregulated in simvastatin-treated preadipocytes compared to nontreated preadipocytes 18-, 35- and 1.7-fold, respectively. In OFs, similar effects of CSE were seen on the expression of CYR61 (1.4-fold) and PTGS2 (3-fold). Simvastatin downregulated adipogenesis, PPAR-γ (2-fold) and SCD (27-fold) expression in OFs. Conclusion: CSE upregulated early adipogenic genes in both mouse 3T3-L1 preadipocytes and human OFs but did not by itself induce adipogenesis. Simvastatin inhibited the expression of both early and late adipogenic genes and adipogenesis in preadipocytes and human OFs. The effect of simvastatin should be investigated in a clinical trial of patients with GO.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cigarette smoke extract (CSE), CYR61, Graves’ opthalmopathy (GO), Orbital fibroblasts, Simvastatin
in
Endocrine Connections
volume
8
issue
9
pages
10 pages
publisher
BioScientifica Ltd.
external identifiers
  • scopus:85073422812
ISSN
2049-3614
DOI
10.1530/EC-19-0319
language
English
LU publication?
yes
id
cfb0c6d3-619f-495d-a328-b69732f2edbb
date added to LUP
2019-10-29 10:00:25
date last changed
2019-11-25 09:35:25
@article{cfb0c6d3-619f-495d-a328-b69732f2edbb,
  abstract     = {<p>Background: Smoking is a strong risk factor for the development of Graves’ ophthalmopathy (GO). Immediate early genes (IEGs) are overexpressed in patients with active GO compared to healthy controls. The aim of this study was to study the effects of tobacco smoking and simvastatin on preadipocytes and orbital fibroblasts (OFs) in the adipogenic process. Methods: Cigarette smoke extract (CSE) was generated by a validated pump system. Mouse 3T3-L1 preadipocytes or OFs were exposed to 10% CSE with or without simvastatin. Gene expression was studied in preadipocytes and OFs exposed to CSE with or without simvastatin and compared to unexposed cells or cells treated with a differentiation cocktail. Results: In 3T3-L1 preadipocytes, Cyr61, Ptgs2, Egr1 and Zfp36 expression levels were two-fold higher in cells exposed to CSE than in unexposed cells. Simvastatin downregulated the expression of these genes (1.6-fold, 5.5-fold, 3.3-fold, 1.4-fold, respectively). CSE alone could not stimulate preadipocytes to differentiate. Scd1, Ppar-γ and adipogenesis were downregulated in simvastatin-treated preadipocytes compared to nontreated preadipocytes 18-, 35- and 1.7-fold, respectively. In OFs, similar effects of CSE were seen on the expression of CYR61 (1.4-fold) and PTGS2 (3-fold). Simvastatin downregulated adipogenesis, PPAR-γ (2-fold) and SCD (27-fold) expression in OFs. Conclusion: CSE upregulated early adipogenic genes in both mouse 3T3-L1 preadipocytes and human OFs but did not by itself induce adipogenesis. Simvastatin inhibited the expression of both early and late adipogenic genes and adipogenesis in preadipocytes and human OFs. The effect of simvastatin should be investigated in a clinical trial of patients with GO.</p>},
  author       = {Shahida, B. and Johnson, P. Sahlstrand and Jain, R. and Brorson, H. and Åsman, P. and Lantz, M. and Planck, T.},
  issn         = {2049-3614},
  language     = {eng},
  number       = {9},
  pages        = {1230--1239},
  publisher    = {BioScientifica Ltd.},
  series       = {Endocrine Connections},
  title        = {Simvastatin downregulates adipogenesis in 3T3-l1 preadipocytes and orbital fibroblasts from graves’ ophthalmopathy patients},
  url          = {http://dx.doi.org/10.1530/EC-19-0319},
  doi          = {10.1530/EC-19-0319},
  volume       = {8},
  year         = {2019},
}