Poster Topical Area: Nutritional Immunology

Location: Hall D

Poster Board Number: 826

E13-01 - Docosahexaenoic acid-derived metabolites regulate bone marrow and splenic B cell populations in obesity in a sex-specific manner

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives:

Obesity is associated with poor immunological outcomes including an impaired B cell response. However, the mechanism by which obesity dysregulates B cell activity and whether this impairment is sex-specific is not clear. Recent data suggests that specialized pro-resolving lipid mediator (SPM) precursors and SPMs synthesized from docosahexaenoic acid (DHA) regulate select B cell populations upon antigen exposure. Therefore, we investigated if SPMs target B cell populations in the context of obesity in a sex-specific manner.


Methods:

C57BL/6 male and female mice were fed lean or obesogenic diets for 15 weeks. Lean and obese male mice were administered a cocktail of SPMs and precursors for four consecutive days. Flow cytometry was used to analyze splenic and bone marrow B cell subsets. Targeted metabolipidomics were used to quantify SPMs.


Results:

Our results revealed that obese male mice had decreased percentages and frequencies of select B cell subsets in the bone marrow and spleen. Furthermore, metabolipidomic analyses showed obese mice had reduced levels of the D-series SPM precursors, 14-HDHA and 17-HDHA as well as the SPM, Protectin DX (PDX). Administration of these deficient SPM precursors and SPMs over the course of four consecutive days resulted in the rescue of specific B cell subsets in the bone marrow and spleen of obese male mice. On the contrary, obese female mice showed modest modifications in the percentages and frequencies of B cell subsets in the bone marrow and spleen. Obese female mice displayed no SPM deficiencies and had elevated levels of ex vivo IL-10 suggesting a protective B cell phenotype.


Conclusions:

The results reveal that B cell phenotypes differ among male and female obese mice, which could be driven by the bioavailability of SPMs to regulate the development of select B cell subsets.




Funding Source: NIH R01AT008375 (S.R.S), NIH S10RR026522 (N.R.), and NIH UL1TR001082 (N.R.)

CoAuthors: William Guesdon – East Carolina University, Brody School of Medicine; Rasagna Kosaraju – East Carolina University, Brody School of Medicine; Michael Armstrong – University of Colorado at Denver; Nichole Reisdorph – University of Colorado at Denver; Saame Raza Shaikh – University of North Carolina at Chapel HIll

Miranda J. Crouch

Graduate Student Researcher
East Carolina University, Brody School of Medicine
Chapel Hill, North Carolina