FP15-4 Resveratrol Inhibits Inflammation-induced Fibrosis in Human Adipocytes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP15-Adipocyte Biology
Bench to Bedside
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 303 (Moscone Center)

Poster Board SUN-672
Ivana Zagotta*1, Daniel Tews1, Hansjoerg Habisch1, Shaoxia Zhou1, Klaus-Michael Debatin1, Martin Wabitsch1 and Pamela Fischer-Posovszky2
1University Medical Center Ulm, 2University Medical Center Ulm, Ulm, Germany
Introduction: Upon excessive expansion as seen in obesity, adipose tissue is infiltrated by macrophages and shows signs of fibrosis ultimately leading to the development of adipose tissue and systemic insulin resistance. A supplementation with resveratrol can reverse the metabolic disturbances in human obesity, in part by mimicking the effects of caloric restriction. We hypothesized that the beneficial effects of resveratrol might be mediated by its anti-fibrotic effect on adipocytes.

Methods: To mimic adipose tissue fibrosis we incubated SGBS adipocytes with increasing doses of THP-1 macrophage conditioned medium in the presence or absence of 100 µM resveratrol. Fibronectin (FN) and collagen 1A1 (col1A1) were studied as markers of fibrosis.

Results: Treatment with 10% MacCM resulted in upregulation of FN (~3.5 fold) and col1A1 (~2.1 fold) mRNA in adipocytes. The same effect was detected on the protein level. This was completely inhibited by coincubation with resveratrol. In order to elicudate the molecular pathway involved, we took advantage of small molecule inhibitors targeting either Sirt1 or PI3K. Interestingly, inhibition of Sirt1 with sirtinol (10 µM) didn't interfere with the effects of resveratrol, indicating that Sirt1 is not involved in mediating the effects of resveratrol on adipocyte fibrosis. Inhibition of PI3K with Ly294002 (20 µM) however, prevented the MacCM-induced upregulation of FN and Col1A1 mRNA expression. Western blot analysis revealed that MacCM induced phosphorylation of Akt and its downstream targets GSK3β, FOXO1 and mTOR, which was again inhibited by resveratrol.

Summary & conclusion: We show that resveratrol inhibits the inflammation-induced development of fibrosis in adipocytes, mediating its anti-fibrotic effect by involving the PI3K/Akt pathway. Taken together, our results demonstrate that resveratrol has health beneficial effects on human adipocytes. Preventing proinflammatory conditions and fibrosis in adipose tissue might be a useful strategy to prevent the development of insulin resistance in the obese state.

Nothing to Disclose: IZ, DT, HH, SZ, KMD, MW, PF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This project is financed by the International Graduate School in Molecular Medicine Ulm (IGradU). PFP recieved a Margarete von Wrangell scholarship financed by the Baden-Wuerttemberg Ministry of Science, Research and Arts, the European Social Fund, and Ulm University.