title: TNFalpha induces and insulin inhibits caspase 3-dependent adipocyte apoptosis.
abstract: Regulation of fat cell number by apoptosis is proposed to be part of a normal physiological cycle in adipose growth and development. To investigate this process, cultured rat adipocytes were treated with various concentrations of tumor necrosis factor alpha (TNFalpha) and/or insulin to determine the roles of these factors in adipocyte apoptosis. The cells were analyzed by flow cytometry using a TUNEL assay. TNFalpha increased adipocyte apoptosis in a dose-dependent fashion. TNFalpha-mediated apoptosis was detectable within 6 h of treatment and continued to increase with time. Decreasing media insulin concentration from 8.5 to 0.85 nM resulted in increased adipocyte apoptosis, whereas high doses of insulin protected adipocytes from TNFalpha-induced apoptosis. TNFalpha-activated apoptosis was accompanied by an increase in caspase 3 activity and could be inhibited by a caspase 3-specific inhibitor. These data suggest that adipose tissue cell number is regulated, in part, by an apoptotic signaling pathway that involves TNFalpha, insulin, and caspase 3.
authors: Department of Foods and Nutrition, University of Georgia, Athens, Georgia 30602, USA.
authors: H
authors: H
authors: Qian
authors: D B
authors: DB
authors: Hausman
authors: M M
authors: MM
authors: Compton
authors: R J
authors: RJ
authors: Martin
authors: M A
authors: MA
authors: Della-Fera
authors: D L
authors: DL
authors: Hartzell
authors: C A
authors: CA
authors: Baile
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D050356:Lipid Metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases