Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2026

Dietary saturated fatty acids impair immune response to Influenza A infection in people living with obesity, increasing interleukin-1β and reducing interferon-⍺. (144419)

Blair J Westbury 1 2 3 , Lily M Williams 1 2 3 , Lisa G Wood 1 2 , Bronwyn S Berthon 1 2 , Hayley A Scott 1 2 , Alexandra C Brown 1 2 , Jay C Horvat 1 2 , Evan J Williams 1 2
  1. Immune Health Research Program, Hunter Medical Research Institute, The University of Newcastle, New Lambton Heights, NSW, Australia
  2. School of Biomedical Science and Pharmacy, The University of Newcastle, Newcastle, New South Wales, Australia
  3. Joint First Author, *

People living with obesity have excess circulating saturated fatty acids (SFAs), and increased risk of severe respiratory viral disease.(1,2)  In patients with asthma, SFAs increased activation of nod-like receptor family-pyrin domain containing 3 (NLRP3) inflammasome(3), while NLRP3 activation is implicated in severe Influenza A virus (IAV) infection.(4) This study aimed to determine if high SFA concentrations contribute to worse respiratory viral disease outcomes in people living with obesity (n=7) compared to healthy-weight controls (n=11). Plasma fatty acids were profiled via gas chromatography and correlated with infection outcomes of Peripheral blood mononuclear cells (PBMCs). PBMCs were treated with a high-dose (2500µM) or low-dose (250µM) of palmitic acid (PA) and infected with IAV. IL-1β was measured as a marker of inflammation and IFN-⍺ for anti-viral activity. PBMCs from people living with obesity treated with the high-dose SFA and infected with IAV produced heightened IL-1β compared to healthy-weight controls [90.0pg/ml (6.7, 332.9) vs. 14.5pg/ml (5.5, 114.5); p=0.004]. A dose-dependent relationship between PA treatment and IFN-⍺ response to IAV was observed. IFN-⍺ production was increased in low-dose PA treatment treated PBMCs from people living with obesity [155.6pg/ml (29.9, 187.2) vs. 59.2pg/ml (4.0, 154.4); p=0.017]. High-dose PA significantly reduced IFN-⍺ response in people living with obesity compared to low-dose PA [6.9pg/ml (2.5, 14.5) vs. 155.6pg/ml (29.9, 187.2); p<0.001]. Systemic monounsaturated fatty acid (MUFA) vaccenic acid were significantly associated with increased IFN-α (r=0.621, p=0.010) and reduced IL-6 production from PBMCs in response to IAV (r=-0.550, p=0.042), while systemic polyunsaturated fatty acid (PUFA) ⍺-linolenic acid correlated with reduced IL-6 production from PBMCs in response to IAV (r=-0.557, p=0.020). Therefore, high doses of SFAs may contribute to more severe inflammation and reduce anti-viral responses to IAV in people living with obesity, exacerbating respiratory viral disease severity. Conversely, certain MUFA and PUFA may exert protective effects against IAV infection.

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