# PREMATURE WEANING AND ADULT CHOLESTEROL HOMEOSTASIS

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 1993 · $107,974

## Abstract

The proposed studies will investigate the effect of premature weaning on
the regulation of cholesterol and lipoprotein metabolism in the adult
guinea pig.  Preliminary studies have shown that weaning 2 day old
neonate guinea pig to a chow diet, as compared to controls weaned at
14-days of age, results in adult guinea pigs with elevated plasma
cholesterol levels, alterations in the composition of plasma low density
lipoproteins (LDL), elevated hepatic HMG-CoA reductase activities, and
reduced expression of hepatic apo B/E receptors.  These data demonstrate
that premature weaning results in a number of significant alterations of
adult lipid metabolism due to a process termed "neonatal imprinting of
metabolic memory".  The proposed studies will expand these observations
to determine the time frame of sensitivity to imprinting by premature
weaning by testing effects of weaning at various time points between 2
and 14 days of age.  Studies will also determine the effect of the
premature weaning diet, saturated versus polyunsaturated fat either low
or high in cholesterol, on the imprinting effects on adult sterol and
lipoprotein metabolism in the guinea pig.  Once the optimal time point
and post-weaning diet have been determined, studies will be performed to
determine the effects of neonatal imprinting by premature weaning on the
homeostatic responses to changes in dietary fat (corn oil versus lard)
and in dietary cholesterol.  Studies will determine the effects on the
regulation of hepatic and extrahepatic sterol synthesis (hepatic HMGCoA
reductase activity, mass and mRNA levels; [3H]water incorporation into
sterols), of low density lipoprotein (LDL) metabolism (hepatic apo B/E
receptor levels, mass and mRNA; in vivo LDL kinetics and tissue uptake),
and of other key parameters modulating endogenous sterol and lipoprotein
metabolism (plasma cholesteryl ester transfer activity and hepatic
cholesterol 7alpha-hydroxylase activity).  These studies will determine
the neonatal imprinting induced changes in hepatic sterol metabolism,
plasma LDL kinetics and cholesteryl ester transfer, and modifications in
gene regulation.  The final set of studies will evaluate the metabolic
changes induced by premature weaning in guinea pigs between the ages of 2
and 14 days.  These studies are designed to investigate the effects of
premature weaning on adult sterol and LDL metabolism in order to better
understand the effects of breast feeding versus premature weaning as
related to elevated plasma LDL cholesterol levels and resulting from
decreased apo B/E receptor expression.

## Key facts

- **NIH application ID:** 2198718
- **Project number:** 5R01HD022954-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **SAM.gov UEI:** ED44Y3W6P7B9
- **Principal Investigator:** DONALD J MC NAMARA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $107,974
- **Award type:** 5
- **Project period:** 1991-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198718

## Citation

> US National Institutes of Health, RePORTER application 2198718, PREMATURE WEANING AND ADULT CHOLESTEROL HOMEOSTASIS (5R01HD022954-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198718. Licensed CC0.

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