Oral Presentation 49th Nutrition Society of Australia Annual Scientific Meeting 2025

Saturated fatty acids increase interleukin-1β and reduce interferon-⍺ in response to influenza A infection in people living with obesity (129344)

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

Obesity affects >30% of Australian adults and is associated with excess circulating nutrients, particularly saturated fatty acids (SFAs), contributing to chronic low-grade systemic inflammation.(1,2) People living with obesity have an increased risk of severe respiratory viral disease, highlighted by the recent SARS-CoV-2 and 2009 H1N1 pandemics.(3,4) Previously, we have shown that consuming a meal high in SFAs increases activation of the NLRP3 inflammasome in the airways of adults with asthma,(5) with others showing that increased NLRP3 activation is implicated in the pathogenesis of severe inflammation during influenza A virus (IAV)-induced lung disease.(6)  Pro-interleukin-1β is cleaved via the NLRP3 inflammasome complex to interleukin (IL)-1β, and so can indicate inflammasome activity. We have shown that SFAs increase pro-inflammatory IL-6 and reduce anti-viral interferon (IFN)-λ production in response to IAV infection in a human epithelial cell line (BCi-NS1.1), which indicates a heightened inflammatory and impaired anti-viral response to infection.(7) This study aimed to determine if high systemic SFAs contribute to worse respiratory viral disease outcomes. PBMCs from people with obesity (n = 7) and healthy-weight controls (n = 11) were treated with a high-dose (2500µM) or low-dose (250µM) of palmitic acid and infected with IAV; and IL-1β and IFN-⍺ were measured as markers of inflammation and anti-viral activity. Plasma fatty acids were profiled via gas chromatography and correlated with infection outcomes of PBMCs. PBMCs from people with obesity treated with high-dose and infected with IAV produced significantly heightened IL-1β compared to healthy weight controls [90.0 pg/ml (6.7, 332.9) vs. 14.5 pg/ml (5.5, 114.5); p = 0.004]. There was a dose-dependent relationship between palmitic acid treatment and anti-viral IFN-⍺ production in response to IAV. IFN-⍺ production was higher in response to low-dose treatment compared to untreated PBMCs from people with obesity [155.6 pg/ml (29.9, 187.2) vs. 59.2 pg/ml (4.0, 154.4); p = 0.017]. Whereas high-dose treatment significantly reduced IFN-⍺ in people with obesity compared to low-dose treatment [6.9 pg/ml (2.5, 14.5) vs. 155.6 pg/ml (29.9, 187.2); p < 0.001. We found higher levels of plasma monounsaturated fatty acid (MUFA), vaccenic acid, to be significantly associated with higher IFN-α (r = 0.621, p = 0.010) and lower IL-6 production from PBMCs in response to IAV (r = -0.550, p = 0.042). Higher plasma polyunsaturated fatty acid (PUFA), ⍺-linolenic acid, was correlated with reduced IL-6 response to IAV (r = -0.557, p = 0.020). This data implicates that high doses of palmitic acid contribute to more severe inflammation in people with obesity in response to IAV and reduces anti-viral responses to IAV in people with obesity, potentially exacerbating respiratory viral disease severity. Conversely, certain MUFA and PUFA may exert protective effects in the context of IAV infection.

  1. Australian Government, AIHW (2024)
  2. Frasca, B. et al. (2017) Front Immunol 8,1003
  3. Popkin, B.M. et al. (2020) Obes Rev 21,e13128
  4. Louie J.K. et al. (2011) Clin Infect Dis 52,301-312
  5. Wood, L. et al. (2019) J Allergy Clin Immunol 143,305-315
  6. Tate, M.D. et al. (2016) Sci Rep 6,27912
  7. Westbury, B.J. & Williams, E.J. et al. (2024) NSA