# PHYSIOLOGICAL FACTORS AFFECTING HUMAN LACTATION

> **NIH NIH R37** · UNIVERSITY OF COLORADO DENVER · 1994 · $213,770

## Abstract

Lipoprotein lipase (LPL) is responsible for hydrolysis of plasma
triglycerides making their component fatty acids available for metabolism
or synthesis into lipid. It plays a major role in the synthesis of milk
fat. Mammary LPL is synthesized and secreted by adipocytes in the
interstitial space of the mammary gland and secreted LPL is dispersed to
be bound by receptors in the capillary wall, the basement membrane and the
basal surface of the mammary alveolar cell. We will characterize the LPL
binding elements present on the surfaces of mammary alveolar cells and in
the mammary extracellular matrix and determine their role in LPL
internalization.  We will test the hypothesis that the plasma
concentration of free fatty acids is an important factor in the activity
of mammary LPL. We will characterize the biochemical nature and the mode
of action of an inhibitor of adipocyte LPL secretion found in conditioned
medium from mammary epithelial cells. Studies from other laboratories
suggest that LPL has a second mode of action, binding lipoproteins to both
cell surface and interstitial heparan sulfate proteogIycans. This
observation suggests the exciting possibility that the high concentrations
of LPL observed immunocytochemically in the lactating mammary gland may
play a role in the transfer of sterol rich VLDL and LDL into the mammary
alveolar cell providing insight into the previously uncharacterized
passage of cholesterol, Vitamin E, beta-carotene and other lipid-soluble
molecules into milk. We will use our model mammary culture systems to
evaluate this hypothesis.

This laboratory is the only one addressing the regulation of LPL in the
mammary gland. An understanding of the regulation of mammary LPL should
give us insight into the regulation of the lipid content of both human and
cow's milk. If the inhibitor of adipocyte LPL that we have identified in
our culture system is active in vivo it may have utility in the reduction
of obesity. Should LPL be involved in the transfer of sterols into the
lactating mammary cell, the possibility of regulating the cholesterol
content of bovine milk can be entertained. Finally, insight into the
interactions of LPL with mammary extracellular matrix molecules may
increase our understanding of the general nature and function of this
important compartment of all secretory organs through which chemical
agents, be they hormones, drugs or toxins, must pass as they travel from
the blood stream to the secretory epithelium.

## Key facts

- **NIH application ID:** 2197838
- **Project number:** 5R37HD019547-10
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** MARGARET Cobb NEVILLE
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $213,770
- **Award type:** 5
- **Project period:** 1990-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197838

## Citation

> US National Institutes of Health, RePORTER application 2197838, PHYSIOLOGICAL FACTORS AFFECTING HUMAN LACTATION (5R37HD019547-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197838. Licensed CC0.

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