Cover Story Current Issue
Weaning involves a dietary switch in mammals, progressively decreasing the reliance on the consumption of a fat-rich milk diet in favour of a carbohydrate-rich diet. Metabolic adaptation to this shift in macronutrient consumption is characterized by reduced hepatic gluconeogenesis, increased liver glycogen content, and changes in lipid metabolism. Such metabolic changes are supported by various nutritional, hormonal, and neuronal factors. Dietary changes during weaning are shown to drive β-cell proliferation and maturation, which is important for the optimal endocrine function of the pancreas. A switch from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5′-adenosine monophosphate-activated protein kinase (AMPK) was found critical for functional maturation of β-cells. Furthermore, changes in the macronutrient composition during the weaning process drive alterations in the gut microbiome, which is essential for the development of immune tolerance. The major calcium absorption pathway also changes during weaning, from the paracellular pathway during the suckling stage to the vitamin D dependent transcellular pathway post-weaning. However, the factors that regulate these post-weaning metabolic adaptations are not fully understood.
Current Issue
Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice
Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice
Objective
Maternal obesity is increasingly common and negatively impacts offspring health. Children of mothers with obesity are at higher risk of developing diseases linked to hematopoietic system abnormalities and metabolism such as type 2 diabetes. Interestingly, disease risks are often dependent on the offspring's sex, suggesting sex-specific reprogramming effect of maternal obesity on offspring hematopoietic stem and progenitor cell (HSPC) function. However, the impact of maternal obesity exposure on offspring HSPC function, and the capability of HSPC to regulate offspring metabolic health is largely understudied. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health.
Methods
We first assessed bone marrow hematopoietic stem and progenitor cell phenotype using postnatal day 21 (P21) and 8-week-old C57BL/6J mice born to control and diet-induced obese dams. We also sorted HSPC (Lineage-, Sca1+, cKit + cells) from P21 mice for competitive primary and secondary transplant, as well as transcriptomic analysis. Body weight, adiposity, insulin tolerance test and glucose tolerance tests were performed in primary and secondary transplant recipient animals.
Results
We discovered sex-differences in offspring HSPC function in response to maternal obesity exposure, where male offspring of obese dams (MatOb) showed decreased HSPC numbers and engraftment, while female MatOb offspring remained largely unaffected. RNA-seq revealed immune stimulatory pathways in female MatOb offspring. Finally, only recipients of male MatOb offspring HSPC exhibited glucose intolerance.
Conclusions
This study demonstrated the lasting effect of maternal obesity exposure on offspring HSPC function and implicates HSPC in metabolic regulation.
Articles in Press
Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice
Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice
Objective
Maternal obesity is increasingly common and negatively impacts offspring health. Children of mothers with obesity are at higher risk of developing diseases linked to hematopoietic system abnormalities and metabolism such as type 2 diabetes. Interestingly, disease risks are often dependent on the offspring's sex, suggesting sex-specific reprogramming effect of maternal obesity on offspring hematopoietic stem and progenitor cell (HSPC) function. However, the impact of maternal obesity exposure on offspring HSPC function, and the capability of HSPC to regulate offspring metabolic health is largely understudied. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health.
Methods
We first assessed bone marrow hematopoietic stem and progenitor cell phenotype using postnatal day 21 (P21) and 8-week-old C57BL/6J mice born to control and diet-induced obese dams. We also sorted HSPC (Lineage-, Sca1+, cKit + cells) from P21 mice for competitive primary and secondary transplant, as well as transcriptomic analysis. Body weight, adiposity, insulin tolerance test and glucose tolerance tests were performed in primary and secondary transplant recipient animals.
Results
We discovered sex-differences in offspring HSPC function in response to maternal obesity exposure, where male offspring of obese dams (MatOb) showed decreased HSPC numbers and engraftment, while female MatOb offspring remained largely unaffected. RNA-seq revealed immune stimulatory pathways in female MatOb offspring. Finally, only recipients of male MatOb offspring HSPC exhibited glucose intolerance.
Conclusions
This study demonstrated the lasting effect of maternal obesity exposure on offspring HSPC function and implicates HSPC in metabolic regulation.
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12th Helmholtz
Diabetes Conference
22-24. Sep, Munich
2022 impact factor: 6.6
You are what you eat
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