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NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα
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Harte, A. L., Tripathi, Gyanendra, Piya, Milan K., Barber, T. M., Clapham, John C., Al-Daghri, Nasser, Al-Disi, Dara, Kumsaiyai, Warunee, Saravanan, Ponnusamy, Fowler, Anne E., O'Hare, J. Paul, Kumar, Sudhesh and McTernan, P. G. (2013) NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα. Obesity research, 21 (11). pp. 2322-23300. doi:10.1002/oby.20336 ISSN 1071-7323.
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Official URL: http://dx.doi.org/10.1002/oby.20336
Abstract
Objective
Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk.
Design and methods
This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques.
Results
Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion.
Conclusions
These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Obesity -- physiological aspects, Adipose tissues, Inflammation | ||||||||||||||||||
| Journal or Publication Title: | Obesity research | ||||||||||||||||||
| Publisher: | Wiley-Blackwell Publishing Ltd. | ||||||||||||||||||
| ISSN: | 1071-7323 | ||||||||||||||||||
| Official Date: | 21 November 2013 | ||||||||||||||||||
| Dates: |
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| Volume: | 21 | ||||||||||||||||||
| Number: | 11 | ||||||||||||||||||
| Page Range: | pp. 2322-23300 | ||||||||||||||||||
| DOI: | 10.1002/oby.20336 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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