Endocrine Abstracts (2012) 28 P213

Chronic or intermittent exposure to Oleic acid (MUFA) induces a greater NF[kappa]B activated inflammatory response than Eicosapentaenoic acid (PUFA) in differentiated human adipocytes

Milan Piya1, Alison Harte1, Kirsty McGee1, Narendra Reddy1, Gyanendra Tripathi1, Philip McTernan1 & Sudhesh Kumar1

1Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, United Kingdom; 2Warwick Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire, Coventry, United Kingdom.

Replacement with mono-unsaturated fatty acids (MUFA) or poly-unsaturated fatty acids (PUFA) reduces inflammation in the pre-diabetic subjects but the benefits are unclear in subjects with type 2 diabetes mellitus (T2DM). Our aim was to investigate whether saturated fatty acids (SFA), MUFA and PUFA produce a similar adipocyte inflammatory response, which may explain the rationale for maintained systemic inflammation noted in subjects with T2DM. The differentiated human preadipocyte cell line (Chub-S7) were treated chronically (48 h) with SFA (10 µM,100 µM), MUFA (1 µM,10 µM) and PUFA (1 µM,10 µM), or exposed to the aforementioned treatment regimen intermittently (INT) for 12 h periods, with alternating rest periods of 12 h for 48 h (n=4). Key components of the innate immune pathway were evaluated over time (0 h-48 h). MUFA treated Chub-S7 cells induced greater IL-6 secretion than PUFA treated cells (IL-6 Chronic; Control:48 h (Mean±SEM):511±17 pg/mL, 10 µM PUFA:48 h:862±147 pg/mL ↑*, 10µM MUFA:48 h:3228±127 pg/mL ↑***,↑#; INT; Control:48 h:589±20 pg/mL, 10 µM PUFA:48 h:484±38 pg/mL ↓*, 10 µM MUFA:48 h:1568±93 pg/mL ↑***,↑#;(*P<0.05 vs control, ***P<0.001 vs control, #P<0.001 vs PUFA). NFκB activity showed a similar pattern with greater activity in MUFA treated cells (NFκB Chronic; Control:48 h:0.051±0.02 ng/µL, 10 µM PUFA:48 h:0.009±0.002 ng/µL ↓*, 10 µM MUFA:48 h:0.11±0.01 ng/µL ↑**,↑#; INT; Control:48 h: 0.079±0.02 ng/µL, 10 µM PUFA:48 h:0.008±0.002ng/µL ↓***, 10 µM MUFA: 48 h:0.102±0.01 ng/µL ↑**,↑#;(**P<0.01 vs control). Chronic SFA treated cells induced cumulative IL-6 secretion (100 µM SFA:12 h: 2122±166 pg/mL vs 48 h: 11,159±962 pg/mL ↑***), whilst low dose had a reduced induction (10 µM SFA:12 h: 261±29 pg/mL vs 48 h: 1464±163 pg/mL ↑***). Again NFκB activity was activated in both conditions at 48 h, and for 100 µM at 12 h (P<0.05). In summary, MUFA induced a heightened adipocyte inflammatory response compared to PUFA conditions. SFAs induced adipocyte inflammation at higher concentrations resulting in substantial cumulative IL-6 release. These studies suggest that replacement of SFA with PUFA may be beneficial in subjects with obesity and T2DM where adipocyte inflammation is exacerbated, whilst replacement with MUFA may not necessarily lead to similar advantageous effects.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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