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

Phillips, E. A.; Alharithi, Y. J.; Kadam, L.; Coussens, L. M.; Kumar, S.; Maloyan, A.

doi:10.1101/2023.11.29.569274

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bioRxiv · 10.1101/2023.11.29.569274

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

Phillips, E. A.·Alharithi, Y. J.·Kadam, L.·Coussens, L. M.·Kumar, S.·Maloyan, A.

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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. 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, and reduction in levels of amino acids, a phenomenon previously linked to aging. Furthermore, in the bone marrow of three-week-old offspring of high-fat diet-fed mothers, we identified a unique B cell population expressing CD19 and CD11b, and found increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11bhi B cells, with all the populations being significantly more abundant in offspring of dams fed HFD but not a regular diet. 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.

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Phillips, E. A., Alharithi, Y. J., Kadam, L., Coussens, L. M., Kumar, S., Maloyan, A.. 2023-12-01. Metabolic abnormalities in the bone marrow cells of young offspring born to obese mothers. https://doi.org/10.1101/2023.11.29.569274

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