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United States Department of Agriculture

Agricultural Research Service

Title: Tumor Necrosis Factor Alpha and Glucocorticoid Synergistically Increase Leptin Production in Human Adipose Tissue: Role for P38 Mitogen-Activated Protein Kinase

Authors
item Trujillo, Maria - DEPT NUTR SCI, RUTGERS UN
item Lee, Mi-Jeong - DEPT NUTR SCI, RUTGERS UN
item Sullivan, Sean - DEPT NUTR SCI, RUTGERS UN
item Feng, Jianying - DEPT NUTR SCI, RUTGERS UN
item Schneider, Stephen - UNIV MED DENTISTRY OF NJ
item Greenberg, Andrew
item Fried, Susan - UNIV MD, SCH OF MED, BALT

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 30, 2005
Publication Date: April 1, 2006
Repository URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16403817&query_hl=15&itool=pubmed_docsum
Citation: Trujillo, M.E., Lee, M., Sullivan, S., Feng, J., Schneider, S.H., Greenberg, A.S., Fried, S.K. 2006. Tumor necrosis factor alpha and glucocorticoid synergistically increase leptin production in human adipose tissue: role for p38 mitogen-activated protein kinase. Journal of Endocrinology and Metabolism. 91(4):1484-90. Epub 2006 Jan 10.

Interpretive Summary: TNF is an inflammatory cytokine that is overexpressed in fat tissue in obesity. The overexpression of TNF in fat tissue is involved in many of the metabolic perturbations associated with obesity and diabetes. TNF increases the neurotransmitter leptin in humans in vivo (meaning within a living organism) but previous studies show it decreases leptin in vitro (or in an environment outside a living organism). To determine the effect of TNF on leptin release from human fat tissue from healthy subjects undergoing elective surgery or needle aspirations of fat tissue at a university hospital. Human subcutaneous fat tissue fragments from non-obese and obese subjects were placed in organ culture with or without TNF added in the presence or absence of insulin and/or a synthetic glucocorticoid (called dex) for up to 2 days. In the absence of hormones, culture with TNF decreased leptin release. In contrast, when added in the presence of dex, TNF increased secreted leptin in adipose tissue from non-obese and obese subjects. The TNF+dex stimulated increase in leptin was associated with an increase in MAPK activity, which regulates many cellular processes and is activated in response to extracellular stimuli, and was totally blocked by MAPK inhibitors. The combined effects of increased local or systemic TNF in combination with glucocorticoids may contribute to increased leptin expression in response to stress that can include infection and obesity.

Technical Abstract: TNF increases plasma leptin in humans in vivo, but previous studies showed it decreases leptin in vitro. The objective of this study was to determine the effect of TNF on leptin release from human adipose tissue (AT) from healthy subjects undergoing elective surgery or needle aspirations of AT at a university hospital. Human omental and abdominal sc AT fragments from non-obese and obese subjects were placed in organ culture without or with TNF added in the presence or absence of insulin and/or dexamethasone (dex; a synthetic glucocorticoid) for up to 2 d. In the absence of hormones, culture with TNF decreased leptin release. In contrast, when added in the presence of dex, TNF increased secreted leptin and leptin mRNA abundance in AT from non-obese and obese subjects. The TNF+dex-stimulated increase in leptin was associated with an increase in p38 MAPK activity and was totally blocked by p38 MAPK inhibitors. In contrast, inhibition of p38 MAPK only partially blocked the effect of TNF on IL-6 production. Culture of obese AT with either p38 or p44/42 MAPK inhibitors also blunted the spontaneous increase in media leptin that occurred from d 1–2 of culture in omental AT of obese subjects. Synergistic effects of increased local or systemic TNF in combination with glucocorticoids may contribute to increased leptin expression in response to stress, including infection and obesity.

Last Modified: 11/22/2014
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