Metabolic abnormalities in the bone marrow cells of young offspring born to mothers with obesity

Abstract

Background/objectives: Intrauterine metabolic reprogramming occurs in mothers with obesity during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet-induced obesity that recapitulates the metabolic changes seen in humans born to women with obesity.

Methods: Here, we profiled and compared the metabolic characteristics of bone marrow cells of newly weaned 3-week-old offspring of dams fed either a high-fat (Off-HFD) or a regular diet (Off-RD). We utilized a state-of-the-art flow cytometry, and targeted metabolomics approach coupled with a Seahorse metabolic analyzer.

Results: We revealed significant metabolic perturbation in the offspring of HFD-fed vs. RD-fed dams, including utilization of glucose primarily via oxidative phosphorylation. We also show a reduction in levels of amino acids, a phenomenon previously linked to bone marrow aging. Using flow cytometry, we found changes in the immune complexity of bone marrow cells and identified a unique B cell population expressing CD19 and CD11b in the bone marrow of three-week-old offspring of high-fat diet-fed mothers. Our data also revealed increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11b^hi B cells.

Conclusions: Altogether, we demonstrate that the offspring of mothers with obesity show metabolic and immune changes in the bone marrow at a very young age and prior to any symptomatic metabolic disease.