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The Influence of Maternal High Fat Diet During Lactation on Offspring
Hematopoietic Priming.
Authors Kim K, Varghese M, Sun H, Abrishami S, Bowers E, Bridges D, Meijer JL, Singer K,
Gregg B
Submitted By Submitted Externally on 3/15/2024
Status Published
Journal Endocrinology
Year 2023
Date Published 11/1/2023
Volume : Pages 165 : Not Specified
PubMed Reference 38048597
Abstract Obesity and metabolic diseases are rising among women of reproductive age,
increasing offspring metabolic risk. Maternal nutritional interventions during
lactation present an opportunity to modify offspring outcomes. We previously
demonstrated in mice that adult male offspring have metabolic impairments and
increased adipose tissue macrophages (ATM) when dams are fed high fat diet (HFD)
during the postnatal lactation window (HFD PN). We sought to understand the
effect of HFD during lactation on early-life inflammation. HFD PN offspring were
evaluated at postnatal day 16 to 19 for tissue weight and gene expression.
Profiling of adipose tissue and bone marrow immune cells was conducted through
lipidomics, in vitro myeloid colony forming unit assays, and flow cytometry. HFD
PN mice had more visceral gonadal white adipose tissue (GWAT) and subcutaneous
fat. Adipose tissue RNA sequencing demonstrated enrichment of inflammation,
chemotaxis, and fatty acid metabolism and concordant changes in GWAT lipidomics.
Bone marrow (BM) of both HFD PN male and female offspring had increased
monocytes (CD45+Ly6G-CD11b+CD115+) and B cells (CD45+Ly6G-CD11b-CD19+).
Similarly, serum from HFD PN offspring enhanced in vitro BM myeloid colonies in
a toll-like receptor 4-dependent manner. We identified that male HFD PN
offspring had increased GWAT pro-inflammatory CD11c+ ATMs (CD45+CD64+). Maternal
exposure to HFD alters milk lipids enhancing adiposity and myeloid inflammation
even in early life. Future studies are needed to understand the mechanisms
driving this pro-inflammatory state of both BM and ATMs, the causes of the
sexually dimorphic phenotypes, and the feasibility of intervening in this window
to improve metabolic health.


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