Affiliation:
1. Departments of Medicine, Addenbrooke's Hospital Cambridge, England, U.K.
2. Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital Cambridge, England, U.K.
3. Department of Pathology, University of Queensland Herston, Australia
4. Department of Diabetes and Endocrinology, Princess Alexandra Hospital Woolloongabba, Australia
Abstract
Tumor necrosis factor-α (TNF-α) production by adipocytes is elevated in obesity, as shown by increased adipose tissue TNF-α mRNA and protein levels and by increased circulating concentrations of the cytokine. Furthermore, TNF-α has distinct effects on adipose tissue including induction of insulin resistance, induction of leptin production, stimulation of lipolysis, suppression of lipogenesis, induction of adipocyte dedifferentiation, and impairment of preadipocyte differentiation in vitro. Taken together, these effects all tend to decrease adipocyte volume and number and suggest a role for TNF-α in limiting increase in fat mass. The aim of the present study was to determine if TNF-α could induce apoptosis in human adipose cells, hence delineating another mechanism by which the cytokine could act to limit the development of, or extent of, obesity. Cultured human preadipocytes and mature adipocytes in explant cultures were exposed in vitro to human TNF-α at varying concentrations for up to 24 h. Apoptosis was assessed using morphological (histology, nuclear morphology following acridine orange staining, electron microscopy) and biochemical (demonstration of internucleosomal DNA cleavage by gel electrophoresis and of annexin V staining using immunocytochemistry) criteria. In control cultures, apoptotic indexes were between 0 and 2.3% in all experiments. In the experimental systems, TNF-α induced apoptosis in both preadipocytes and adipocytes, with indexes between 5 and 25%. Therefore, TNF-α induces apoptosis of human preadipocytes and adipocytes in vitro. In view of the major metabolic role of TNF-α in human adipose tissue, and the knowledge that adipose tissue is dynamic (with cell acquisition via preadipocyte replication/differentiation and cell loss via apoptosis), these findings describe a further mechanism whereby adipose tissue mass may be modified by TNF-α.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
171 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献