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PMID: 7738178 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.

The Journal of clinical investigation ·Vol. 95 ·No. 5 ·1995-05-00 ·Pages 2111-9

Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB

Abstract

A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.

MeSH Terms
Adipocytes/metabolism Adipose Tissue/metabolism,pathology,physiopathology Adult Biopsy Blotting, Northern Body Mass Index Cells, Cultured Enzyme-Linked Immunosorbent Assay Female Gene Expression Regulation Humans Lipoprotein Lipase/metabolism Male Middle Aged Obesity/metabolism,physiopathology Polymerase Chain Reaction RNA, Messenger/analysis,biosynthesis Regression Analysis Tumor Necrosis Factor-alpha/analysis,biosynthesis Weight Loss
Chemicals
RNA, Messenger Tumor Necrosis Factor-alpha Lipoprotein Lipase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kern P A
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Saghizadeh M
Ong J M
Bosch R J
Deem R
Simsolo R B
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117899
Published
1995-05-00
Pages
2111-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295809
Subset
IM
Grants
NIDDK NIH HHS · DK-39176 · United States
NCRR NIH HHS · RR-00425 · United States
External Links
PubMed source DOI: 10.1172/JCI117899 PMC Full Text View journal details
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