Altered Tumor Necrosis Factor-α (TNF-α) Processing in Adipocytes and Increased Expression of Transmembrane TNF-α in Obesity

Author:

Xu Haiyan1,Uysal K. Teoman1,Becherer J. David2,Arner Peter3,Hotamisligil Gökhan S.1

Affiliation:

1. Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts

2. Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Durham, North Carolina

3. Karolinska Institute, Department of Medicine, Huddinge University Hospital, Huddinge, Sweden

Abstract

Tumor necrosis factor-α (TNF-α) is synthesized as a 26-kDa transmembrane protein (mTNF-α), which may present on the cell surface or be processed to release the 17-kDa soluble form (sTNF-α). Because regulation of this ectodomain shedding might be critical in the generation of systemic versus local cytokine responses, we examined the rate of mTNF-α processing in adipocytes and its regulation in obesity. Here, we demonstrate that the 26-kDa mTNF-α is present in adipose tissue and that its production is significantly increased in different rodent obesity models as well as in obese humans. There was no apparent deficiency in the level of the major TNF-α converting enzyme in adipose tissue to account for the excess amount of mTNF-α produced in obesity. However, experiments in cultured fat cells stably expressing TNF-α demonstrated a significantly decreased rate of TNF-α cleavage in differentiated adipocytes compared with preadipocytes. Thus, a decreased processing rate of mTNF-α in mature adipocytes combined with an increase in TNF-α production may be a potential mechanism resulting in elevated membrane-associated TNF-α in adipose tissue in obesity.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3