Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester

To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitam in A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM) -retinyl esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfec ted with a rat CEL cDNA. We also studied tissue uptake of CM-RE in CEL-defi cient mice generated by targeted disruption of the CEL gene. CEL-transfecte d cells secreted active enzyme into the medium. However, both control and C EL-transfected cells accumulated exogenously added CM-RE or CM remnant (CMR )-derived RE in equal amounts. Serum clearance of intravenously injected CM -RE and cholesteryl ester were not different between wild-type and CEL-defi cient mice. Also, the uptake of the two compounds by the liver and other ti ssues did not differ. These data indicate that the lack of CEL expression d oes not affect the uptake of dietary CM-RE by the liver or other tissues. M oreover, the percentage of retinol formed in the liver after CM-RE uptake, the levies of retinol and retinol-binding protein in serum, and retinoid le vels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism and retinoid distribution throughou t the body. Surprisingly, in both pancreas and liver of wild-type, heterozy gous, and homozygous CEL-deficient mice, the levels of bile salt-dependent retinyl ester hydrolase (REH) activity were similar. This indicates that in the mouse pancreas and liver an REH enzyme activity, active in the presenc e of bile salt and distinct from GEL, is present, compatible with the resul ts from our accompanying paper that the intestinal processing and absorptio n of RE were unimpaired in CEL-deficient mice.