The Influence of Maternal High Fat Diet During Lactation on Offspring Hematopoietic Priming

Area of Science:

• Reproductive biology
• Immunology
• Metabolic disease

Background:

• Rising obesity and metabolic diseases in women of reproductive age pose risks to offspring.
• Maternal nutrition during lactation is a critical window for influencing offspring metabolic health.
• Previous studies showed adult male offspring exhibit metabolic impairments after maternal high-fat diet (HFD) during lactation.

Purpose of the Study:

• To investigate the impact of maternal HFD during the lactation period on early-life inflammation in offspring.
• To characterize immune cell profiles and inflammatory markers in offspring exposed to HFD during lactation.

Main Methods:

• Offspring were evaluated at postnatal days 16-19 for tissue weight and gene expression.
• Adipose tissue and bone marrow immune cells were profiled using lipidomics, flow cytometry, and in vitro myeloid colony-forming assays.
• RNA sequencing of adipose tissue was performed to analyze gene expression patterns.

Main Results:

• High-fat diet (HFD) postnatal (PN) offspring exhibited increased visceral and subcutaneous fat.
• Adipose tissue RNA sequencing revealed enrichment in inflammation, chemotaxis, and fatty acid metabolism pathways.
• Bone marrow showed increased monocytes and B cells in both male and female HFD PN offspring.
• Male HFD PN offspring displayed elevated pro-inflammatory CD11c+ adipose tissue macrophages (ATMs).

Conclusions:

• Maternal exposure to HFD during lactation alters milk composition, leading to increased adiposity and myeloid inflammation in early life.
• The findings highlight the critical role of maternal nutrition in programming offspring metabolic and inflammatory phenotypes.
• Further research is needed to elucidate mechanisms, sex-specific differences, and potential interventions.