BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is chronically elevated in the adipose tissue from obese humans and mice. This increase in TNF-alpha contributes to the insulin resistance, elevated plasminogen activator inhibitor-1 (PAI-1) levels, and cardiovascular complications associated with obesity and noninsulin-dependent diabetes (NIDDM). PAI-1 gene expression in adipose tissue is also stimulated by transforming growth factor-beta (TGF-beta). Experiments were performed to determine whether TGF-beta is regulated by TNF-alpha and elevated in obesity. MATERIALS AND METHODS: The concentration of TGF-beta and PAI-1 mRNA in murine adipose tissue and cultured 3T3-L1 adipocytes was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR), and the cellular localization of these molecules was evaluated using in situ hybridization and cell fractionation. Total TGF-beta protein was determined by employing an ELISA assay. RESULTS: TGF-beta mRNA and protein were increased in the adipose tissue from two different strains of genetically obese mice (i.e., ob/ob and db/db), compared with their lean counterparts. This increase in TGF-beta may result from TNF-alpha since TNF-alpha increased TGF-beta mRNA expression in the adipose tissue of lean mice and stimulated TGF-beta production by cultured adipocytes. Administration of TGF-beta increased PAI-1 antigen in the plasma and PAI-1 mRNA in the adipocytes of lean mice, and enhanced the rate of PAI-1 synthesis by adipocytes in vitro. CONCLUSIONS: TNF-alpha contributes to the elevated TGF-beta expression demonstrated in the adipose tissue of obese mice. A potential role for TGF-beta in the increased PAI-1 and vascular pathologies associated with obesity/NIDDM is suggested.
BACKGROUND:Tumor necrosis factor-alpha (TNF-alpha) is chronically elevated in the adipose tissue from obesehumans and mice. This increase in TNF-alpha contributes to the insulin resistance, elevated plasminogen activator inhibitor-1 (PAI-1) levels, and cardiovascular complications associated with obesity and noninsulin-dependent diabetes (NIDDM). PAI-1 gene expression in adipose tissue is also stimulated by transforming growth factor-beta (TGF-beta). Experiments were performed to determine whether TGF-beta is regulated by TNF-alpha and elevated in obesity. MATERIALS AND METHODS: The concentration of TGF-beta and PAI-1 mRNA in murine adipose tissue and cultured 3T3-L1 adipocytes was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR), and the cellular localization of these molecules was evaluated using in situ hybridization and cell fractionation. Total TGF-beta protein was determined by employing an ELISA assay. RESULTS:TGF-beta mRNA and protein were increased in the adipose tissue from two different strains of genetically obesemice (i.e., ob/ob and db/db), compared with their lean counterparts. This increase in TGF-beta may result from TNF-alpha since TNF-alpha increased TGF-beta mRNA expression in the adipose tissue of lean mice and stimulated TGF-beta production by cultured adipocytes. Administration of TGF-beta increased PAI-1 antigen in the plasma and PAI-1 mRNA in the adipocytes of lean mice, and enhanced the rate of PAI-1 synthesis by adipocytes in vitro. CONCLUSIONS:TNF-alpha contributes to the elevated TGF-beta expression demonstrated in the adipose tissue of obesemice. A potential role for TGF-beta in the increased PAI-1 and vascular pathologies associated with obesity/NIDDM is suggested.
Authors: R K Assoian; B E Fleurdelys; H C Stevenson; P J Miller; D K Madtes; E W Raines; R Ross; M B Sporn Journal: Proc Natl Acad Sci U S A Date: 1987-09 Impact factor: 11.205
Authors: Baowen Du; William P Cawthorn; Alison Su; Casey R Doucette; Yao Yao; Nahid Hemati; Sarah Kampert; Colin McCoin; David T Broome; Clifford J Rosen; Gongshe Yang; Ormond A MacDougald Journal: J Biol Chem Date: 2012-12-17 Impact factor: 5.157
Authors: Rosalyn D Abbott; Rebecca Y Wang; Michaela R Reagan; Ying Chen; Francis E Borowsky; Adam Zieba; Kacey G Marra; J Peter Rubin; Irene M Ghobrial; David L Kaplan Journal: Adv Healthc Mater Date: 2016-05-19 Impact factor: 9.933