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Session: Nutritional Proteomics and Metabolomics (Oral 2)

(OR02-02-23) Comparative Proteomic Analysis of Human and Mouse Milk Fat Globules and Membranes Identifies Core Cellular Systems Contributing to Mammary Lipid Trafficking and Secretion

Saturday, July 22, 2023
2:42 PM – 2:54 PM ET
Location:  Constitution B

    Presenting Author(s)

  • Jayne Martin Carli, PhD

    Postdoctoral Fellow
    University of Colorado Anschutz Medical Campus
    Aurora, Colorado, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • JM

    James McManaman, PhD

    University of Colorado Anschutz Medical Campus

  • JM

    Jenifer Monks, PhD

    University of Colorado Anschutz Medical Campus

Disclosure(s):
Jayne Martin Carli, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Human milk delivers critical nutritional and immunological support to the infant. The milk fat globule (MFG) and its enveloping membrane contain many bioactive components, yet the mechanisms regulating MFG production and secretion are poorly understood, especially in humans. We aimed to directly compare the proteomes of human MFG membranes with cytoplasm-containing MFGs, to identify cellular pathways contributing to MFG production and to determine the similarity between MFGs from humans and experimental mouse models.

Methods: In this study, we perform quantitative proteomic profiling of milk fat globules from human and mouse milk, as well as from isolated membranes physically disrupted from human milk fat globules.

Results: Using paired analyses of the human samples we report membrane enrichment of the proteins involved in docking/tethering the lipid droplet to the membrane (butyrophilin subfamily 1 member A1 - BTN1A1, xanthine dehydrogenase – XDH, perilipin 2 – PLIN2, lactalbumin alpha – LALBA) as well as minor components involved in the signaling pathway for secretion. Comparing abundance between human and mouse milk fat globules we find that 8 of the top 20 major milk fat globule proteins are shared between the two species (fatty acid binding protein 3 – FABP3, lactadherin – MFGE8, BTN1A1, PLIN2, XDH, casein alpha s1 – CSN1S1, RAB18, member RAS oncogene family – RAB18 and albumin – ALB). Comparative pathway enrichment analyses between human and mouse samples reveal similarities in shared (neutrophil degranulation, vesicle mediated transport) and distinct (VEGFA-VEGFR2 enriched in human only) membrane trafficking and signaling pathways involved in milk fat secretion.

Conclusions: Our results advance knowledge of the composition and relative quantities of proteins in human and mouse milk fat globules in greater detail, provide a quantitative profile of specifically enriched human milk fat globule membrane proteins, and identify core cellular systems involved in milk lipid secretion.

Funding Sources: National Institute of Child Health and Human Development, American Heart Association