(P30-005-23) Hyperglycemia in Obesity Is Associated With an Increased Production of IL-1β by Antigen-Presenting Cells: Preliminary Data From the Nutrition and Immunity (NutrIMM) Study

Objectives: Obesity and type 2 diabetes (T2D) are associated with systemic inflammation, lower immune function and a higher risk of infection. Hyperglycemia and obesity in T2D patients have been associated with an increased production of interleukin (IL)-1β by adipose tissue macrophages. Yet, it is unclear whether immune dysfunctions are caused by the excess of adiposity and/or hyperglycemia and/or differences in food habits.

The aim of this study was to assess the independent effect of excess adiposity, glycemia and diet on the phenotype and function of antigen-presenting cells (APCs).

Methods: Four groups of adults 1-Lean-normoglycemic (NG; n=31), 2-Obese-NG (n=17), 3-Obese-glucose intolerant (GI; n=21) and 4-Obese-T2D (n=13) consumed a standardized North American diet (35% fat, 48% carbohydrate and 17% protein) for 4 weeks in isocaloric conditions with all meals provided to them. Blood samples were collected in the fasting state before and after the intervention. The proportions of monocytes, dendritic cells (DC) and their activation markers were assessed from whole blood using flow cytometry. The ex vivo production of IL-1β was assessed from isolated peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide.

Results: At baseline, Obese-GI and Obese-T2D had a higher production of IL-1β compared to the lean group while a similar trend was observed post-intervention. Post-intervention, the proportion of monocytes (PBMCs expressing CD14 and HLA-DR) was higher and the proportion of plasmacytoid DC (HLA-DR⁺CD11c^-CD123⁺) was lower in Obese-T2D when compared to the lean group only. The Obese-T2D also had higher proportions of PBMCs expressing CD54 (an activation marker) when compared to the lean group only. Although similar trends were observed in immune cell phenotypes at baseline across groups, it did not reach statistical significance.

Conclusions: Our preliminary data suggest that hyperglycemia increases IL-1β production by APCs to a greater extent than excess adiposity, independently of diet. The increased proportion of circulating monocytes in obesity and T2D likely contributes to the increased cytokine production in that population and disease progression.

Funding Sources: Canadian Institutes of Health Research