Abstract
Omental fat from obese and obese diabetic patients dys‐regulates vascular function by NF‐κB, PARP‐1 and interleukin 12‐dependent mechanism (1076.7)
The FASEB journal, Vol.28(S1), p.n/a
04/2014
DOI: 10.1096/fasebj.28.1_supplement.1076.7
Abstract
Background: The abdominal adipose omental tissue in obese and obese diabetic patients is a major risk factor for cardiovascular diseases. Here we determined the role of interleukin 12 (IL‐12), NFκB and PARP‐1 in omental tissue‐induced vascular dysfunction in obese, obese type 2 diabetic (T2D) patients, and type 2 diabetic (db‐/db‐) mouse.
Methods & results: Mesenteric resistance arteries (MRA) from C57/BL6 and IL‐12 receptor‐/‐ mice were mounted in a wire myograph and incubated with omental fat from obese, obese T2D patients, db‐/db‐ and db‐/db‐p50NFκB‐/‐, db‐/db‐PARP‐1‐/‐ and C57/BL6 mice treated with and without NFκB (DHMQ), PARP‐1 (ABT‐888) inhibitors and IL‐12 receptor antagonist. The endothelium‐dependent relaxation was not affected. However, we observe an increase in phenylephrine‐(PE) and thromboxane‐(U46619)‐induced contraction in MRA incubated with omental fat from obese, obese T2D patients and db‐/db‐ mice. The contraction was potent with omental fat from obese T2D than obese patients. Interestingly, ABT‐888, DHMQ, IL‐12 receptor antagonist and MRA from IL‐12 receptor‐/‐ significantly reduced the exacerbated PE and thromboxane‐induced contraction in MRA incubated with omental fat from obese, obese T2D patients or db‐/db‐. Importantly, PE and thromboxane‐induced contraction was significantly reduced when MRA from db‐/db‐p50NFκB‐/‐ or db‐/db‐PARP‐1‐/‐ double knockout mice were incubated with omental fat from obese, obese T2D patients and db‐/db‐ mice. These results were associated with augmented NFkB and PARP‐1 activity and IL‐12 content in omental fat from obese, obese T2D patients and db‐/db‐ mice compared to control. IL‐12 content was significantly reduced in omental fat incubated with NFkB and PARP‐1 inhibitors.
Conclusion: The present study provide evidence that adipose omental tissue in obese, obese T2D patients and T2D mouse impairs vascular function by IL‐12, NFκB and PARP‐1‐dependent mechanisms
Details
- Title: Subtitle
- Omental fat from obese and obese diabetic patients dys‐regulates vascular function by NF‐κB, PARP‐1 and interleukin 12‐dependent mechanism (1076.7)
- Creators
- Modar Kassan - EVMSNorfolkVAUnited StatesKarima Ait Aissa - EVMSBronson Haynes - EVMSNorfolkVAUnited StatesMark Fontana - SantaraNorfolkVAUnited StatesAnca Dobrian - EVMSNorfolkVAUnited StatesStephen Wohlgemuth - SantaraNorfolkVAUnited StatesMohamed Trebak - Albany State UniversitySouad Belmadani - EVMSNorfolkVAUnited StatesKhalid Matrougui - EVMSNorfolkVAUnited States
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.28(S1), p.n/a
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.28.1_supplement.1076.7
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Internal Medicine; Cardiovascular Medicine
- Record Identifier
- 9984361718902771
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