Elevated expression of transforming growth factor-beta in adipose tissue from obese mice

Mol Med. 1997 Jan;3(1):37-48.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipose Tissue / chemistry*
  • Animals
  • Cell Fractionation
  • Gene Expression Regulation / physiology
  • Insulin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / genetics
  • Obesity / metabolism*
  • Plasminogen Activator Inhibitor 1 / analysis
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics
  • RNA, Messenger / analysis
  • Transforming Growth Factor alpha / pharmacology
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / genetics

Substances

  • Insulin
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta