Metabolic abnormalities in the bone marrow cells of young offspring born to obese mothers.

ABSTRACT

Intrauterine metabolic reprogramming occurs in obese mothers 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 obese women. 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 targeted metabolomics approach coupled with a Seahorse metabolic analyzer. 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 found a reduction in levels of amino acids, a phenomenon previously linked to bone marrow aging. Using flow cytometry, we 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, and found increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11bhi B cells. Altogether, we demonstrate that the offspring of obese mothers show metabolic and immune changes in the bone marrow at a very young age and prior to any symptomatic metabolic disease.