Maternal high-fat diet and obesity compromise fetal hematopoiesis

Ashley N. Kamimae-Lanning, Stephanie Krasnow, Natalya A. Goloviznina, Xinxia Zhu, Quinn R. Roth-Carter, Peter R. Levasseur, Sophia Jeng, Shannon McWeeney, Peter Kurre, Daniel Marks

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high-fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods: We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high-fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results: Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions: Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment.

Original languageEnglish (US)
Pages (from-to)25-38
Number of pages14
JournalMolecular Metabolism
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Hematopoiesis
High Fat Diet
Hematopoietic Stem Cells
Obesity
Mothers
Hematopoietic System
Fetal Stem Cells
Liver
Stem Cells
Transplantation
Genes
Cell Movement
Cell Differentiation
Flow Cytometry
Fetus
Down-Regulation
Diet
Gene Expression

Keywords

  • Developmental programming
  • Fetal liver
  • Hematopoiesis
  • Hematopoietic stem and progenitor cells
  • High-fat diet
  • Obesity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Kamimae-Lanning, A. N., Krasnow, S., Goloviznina, N. A., Zhu, X., Roth-Carter, Q. R., Levasseur, P. R., ... Marks, D. (2015). Maternal high-fat diet and obesity compromise fetal hematopoiesis. Molecular Metabolism, 4(1), 25-38. https://doi.org/10.1016/j.molmet.2014.11.001

Maternal high-fat diet and obesity compromise fetal hematopoiesis. / Kamimae-Lanning, Ashley N.; Krasnow, Stephanie; Goloviznina, Natalya A.; Zhu, Xinxia; Roth-Carter, Quinn R.; Levasseur, Peter R.; Jeng, Sophia; McWeeney, Shannon; Kurre, Peter; Marks, Daniel.

In: Molecular Metabolism, Vol. 4, No. 1, 01.01.2015, p. 25-38.

Research output: Contribution to journalArticle

Kamimae-Lanning, AN, Krasnow, S, Goloviznina, NA, Zhu, X, Roth-Carter, QR, Levasseur, PR, Jeng, S, McWeeney, S, Kurre, P & Marks, D 2015, 'Maternal high-fat diet and obesity compromise fetal hematopoiesis', Molecular Metabolism, vol. 4, no. 1, pp. 25-38. https://doi.org/10.1016/j.molmet.2014.11.001
Kamimae-Lanning AN, Krasnow S, Goloviznina NA, Zhu X, Roth-Carter QR, Levasseur PR et al. Maternal high-fat diet and obesity compromise fetal hematopoiesis. Molecular Metabolism. 2015 Jan 1;4(1):25-38. https://doi.org/10.1016/j.molmet.2014.11.001
Kamimae-Lanning, Ashley N. ; Krasnow, Stephanie ; Goloviznina, Natalya A. ; Zhu, Xinxia ; Roth-Carter, Quinn R. ; Levasseur, Peter R. ; Jeng, Sophia ; McWeeney, Shannon ; Kurre, Peter ; Marks, Daniel. / Maternal high-fat diet and obesity compromise fetal hematopoiesis. In: Molecular Metabolism. 2015 ; Vol. 4, No. 1. pp. 25-38.
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abstract = "Objective: Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high-fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods: We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high-fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results: Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions: Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment.",
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