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Tissue specific changes in acyl-CoA: cholesterol acyltransferase (ACAT) mRNA levels in rabbits
M E Pape1, P A Schultz, T J Rea
1Division of Therapeutics, Parke-Davis Pharmaceutical Research Division, Ann Arbor, MI 48105, USA.
Journal of Lipid Research
|April 1, 1995
Summary
Researchers identified a rabbit acyl-CoA:cholesterol acyltransferase (ACAT) mRNA and found its levels increase in liver and aorta when rabbits consume a high-fat, high-cholesterol diet. This ACAT mRNA expression is regulated by diet and can be lowered by an ACAT inhibitor.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Acyl-CoA:cholesterol acyltransferase (ACAT) plays a crucial role in cellular cholesterol metabolism.
- A human ACAT cDNA clone (K1) was previously identified, enabling further research into ACAT's function and regulation.
- Understanding ACAT's tissue-specific expression and regulation is vital for metabolic and cardiovascular disease research.
Purpose of the Study:
- To isolate and characterize a rabbit cDNA encoding ACAT.
- To investigate the tissue distribution and expression levels of rabbit ACAT mRNA.
- To determine the in vivo regulation of ACAT mRNA levels in response to dietary changes and ACAT inhibition.
Main Methods:
- Screening a rabbit liver cDNA library using a human ACAT clone to isolate rabbit ACAT cDNA (ACAT14b).
- Northern blotting and RNAse protection assays to determine ACAT mRNA expression in various rabbit tissues and cell types.
- In vivo studies involving high-fat/high-cholesterol diets and treatment with an ACAT inhibitor (CI-976) to assess mRNA regulation.
Main Results:
- A 919 bp partial rabbit ACAT cDNA (ACAT14b) was isolated, showing >90% homology to human ACAT.
- ACAT mRNA14b was detected in multiple rabbit organs, with the adrenal gland showing the highest concentration, and hepatic nonparenchymal cells having higher levels than parenchymal cells.
- High-fat/high-cholesterol diet increased hepatic and aortic ACAT mRNA14b levels, while CI-976 treatment reduced these levels in liver and aorta.
Conclusions:
- Rabbit ACAT mRNA14b exhibits a specific tissue distribution, with notable expression in the adrenal gland and liver nonparenchymal cells.
- ACAT mRNA14b levels are significantly upregulated in the liver and aorta in response to dietary fat and cholesterol.
- ACAT mRNA expression in the liver and aorta can be modulated by specific ACAT inhibitors, suggesting a role in cholesterol homeostasis.
