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Maternal obesity and programming of metabolic syndrome in the offspring: searching for mechanisms in the adipocyte progenitor pool

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BMC MEDICINE
卷 21, 期 1, 页码 -

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BMC
DOI: 10.1186/s12916-023-02730-z

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Obesity; Gestational diabetes; Metabolic syndrome; Fetal programming; Adipose tissue

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Recent studies have shown that the quality of adipose tissue, rather than its quantity, contributes to the risk of obesity-related diseases. Adipose-derived stem cells give rise to adipocytes during the development of adipose depots. In adult depots, progenitor cells serve as a reservoir for replacing aging adipocytes and increasing lipid storage capacity.
BackgroundIt is now understood that it is the quality rather than the absolute amount of adipose tissue that confers risk for obesity-associated disease. Adipose-derived stem cells give rise to adipocytes during the developmental establishment of adipose depots. In adult depots, a reservoir of progenitors serves to replace adipocytes that have reached their lifespan and for recruitment to increase lipid buffering capacity under conditions of positive energy balance.MainThe adipose tissue expandability hypothesis posits that a failure in de novo differentiation of adipocytes limits lipid storage capacity and leads to spillover of lipids into the circulation, precipitating the onset of obesity-associated disease. Since adipose progenitors are specified to their fate during late fetal life, perturbations in the intrauterine environment may influence the rapid expansion of adipose depots that occurs in childhood or progenitor function in established adult depots. Neonates born to mothers with obesity or diabetes during pregnancy tend to have excessive adiposity at birth and are at increased risk for childhood adiposity and cardiometabolic disease.ConclusionIn this narrative review, we synthesize current knowledge in the fields of obesity and developmental biology together with literature from the field of the developmental origins of health and disease (DOHaD) to put forth the hypothesis that the intrauterine milieu of pregnancies complicated by maternal metabolic disease disturbs adipogenesis in the fetus, thereby accelerating the trajectory of adipose expansion in early postnatal life and predisposing to impaired adipose plasticity.

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