Abstract
The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins and plays a major role in the catabolism of HDL. Lipoprotein lipase (LPL) is the rate-limiting enzyme for hydrolysis of circulating triglyceride and is involved in HDL formation. We show that tissues containing LPL are major sources of CETP mRNA in several mammalian species, including some with low cholesteryl ester transfer activity in plasma. In hamsters, adipose tissue and heart were found to be the richest sources of both CETP and LPL mRNA; in situ hybridization studies showed that the same cell types (i.e. adipocytes or myocytes) contained CETP and LPL mRNA in these tissues. Isolated adipocytes synthesized active CETP. Dietary studies revealed a complex pattern of response of CETP mRNA levels in different tissues, which showed partial similarity to the changes in LPL mRNA abundance. However, high cholesterol diets resulted in increased CETP mRNA abundance in adipose tissue, heart, and skeletal muscle, without equivalent changes in LPL mRNA. Plasma HDL cholesteryl ester levels showed strong inverse correlations with CETP mRNA abundance in adipose tissue. The results suggest a conserved function of CETP in adipose tissue and heart, such as a co-ordinate action with LPL to enhance HDL turnover. Although there is considerable overlap in the tissue- and cell-specific pattern of CETP and LPL gene expression, dietary studies revealed only limited parallelism in response at the mRNA level. The increase in CETP mRNA in peripheral tissues in response to increased dietary cholesterol suggests that local induction of CETP synthesis may help to recycle cholesterol deposited in these tissues during lipolysis of dietary lipoproteins.
Highlights
Xian Cheng Jiang, Philippe Moulin, Elaine Quinet, Ira J
In order to investigate the distributioonf cholesteryl ester transfer protein (CETP) mRNA in different tissues, the hamsterwas used as a model, since it is a small animal with highlipid transfer activity in plasma
Isolated hamster adipocytes were shown to secrete functionally active CETP, andadipose tissue and heart CETmPRNA levels were correlated with plasma CETP concentration, indicating that peripherally synthesized CETP enters the plasma compartment.Strong inverse correlations of adipose tissue CETP mRNA levels with the concentration of high density lipoproteins (HDL) cholesteryl esters suggest a role for locally synthesized CETP in the catabolism of HDL cholesteryl esters
Summary
Molecular Cloning of the Hamster CETP cDNA-First strand cDNA was synthesized from liver, heart, and adipose tissue mRNA using oligo(dT) as primer. The full-length human CETP cDNA probe was hybridized with the blot at 37 “C for. The blot was washed at 42 “C with a solution containing 1 X SSC and 0.5% SDS and exposed to film for 42 h at -70 “C with intensifying screens. The blot was prepared for the second round of hybridization by washing at 100 “C with a solution containing 0.1 X SSC and 0.1% SDS to remove the bound probe. RNase Protection Analysis-A fragment of the human CETP cDNA (160 base pairs, codons 183-235) was cloned into Bluescript. LipidPTrroatenisnfer mRNA in Fat was prepared from a clone containing a 624-basepair fragment of the mouse LPL cDNA [13].Hamster organs were isolated, fixed, sectioned, and analyzed by in situ hybridization as described previously [13].
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