Pancreatic lipase‐related protein 2 is responsible for the increased hepatic retinyl ester hydrolase activity in vitamin A‐deficient mice

Dietary vitamin A as retinyl ester is hydrolysed and re-esterified with long-chain fatty acids in the small intestine. The esterified vitamin A is subsequently stored in the liver, where it is hydrolysed to free retinol to be transported by carrier proteins to the target tissue. A decreased availability of retinol carrier proteins has been suggested to be responsible for affecting metabolic availability of vitamin A in type 1 diabetes. Using BB Wistar rats, the present study was undertaken to examine whether the presence of a hyperglycaemic state modifies retinyl ester hydrolase (REH) activity in the intestine and the liver. At the onset of diabetes, hepatic REH enzymatic activity was significantly (P<0·05) decreased. However, REH activity remained unaffected in the small intestine, including both ileum and jejunum. Diabetes also resulted in decreased plasma and liver concentrations of retinol. An in vitro study was conducted to examine the effect of diabetes on the intestinal uptake of retinyl palmitate. Jejunum and ileum from diabetic and non-diabetic BB rats were incubated with labelled retinyl palmitate at different concentrations ranging from 32 to 256 nmol/l. The uptake of retinyl palmitate was increased in both diabetic and non-diabetic rats together with the increase of substrate concentration. However, no significant difference was observed in the uptake of retinyl palmitate between diabetic and non-diabetic rats. These present results suggest that the depressed hepatic REH activities may contribute to the diabetes-associated metabolic derangement of vitamin A.

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Flupenthixol and cefotiam: effects on vitamin A metabolism in rats

British Journal Of Nutrition ◽

10.1079/bjn20041236 ◽

2004 ◽

Vol 92 (4) ◽

pp. 597-605 ◽

Cited By ~ 3

Author(s):

Rainer Schindler ◽

Tanja Fielenbach ◽

Gerhard Rave

Keyword(s):

Vitamin A ◽

Retinol Binding Protein ◽

Brown Norway ◽

Early Event ◽

Retinyl Ester ◽

Vitamin A Metabolism ◽

Ester Hydrolase ◽

Retinyl Ester Hydrolase ◽

Plasma Retinol ◽

The Impact

We examined the alterations in vitamin A metabolism as a result of flupenthixol or cefotiam administration. The impact of these drugs on indices of vitamin A status was evaluated in Brown Norway and Long–Evans rats. Intramuscular drug administration for 28 d resulted in a decline in systemic retinol. Changes in circulating retinol with time for chronic dosing showed drug treatment (P<0·001) and time (P<0·03) to be significant factors, but rat strain (P=0·33) was not a significant factor. Flupenthixol was the most active retinol-lowering compound (P<0·005). At the end of the 28 d period, hepatic retinyl ester hydrolase activity was greater in drug-treated rats than in controls (P<0·05). With regard to effects on liver reserves: (1) flupenthixol treatment resulted in vitamin A depletion (P<0·05); (2) cefotiam treatment stimulated vitamin A accumulation; (3) distinctive patterns of retinol and its esters were seen in response to treatment. It is reasonable to assume that the drugs interfere with vitamin A in at least two ways: (1) lowering of plasma retinol, an early event in the interaction, may be caused by inhibition of hepatic holo-retinol-binding protein secretion or stimulation of clearance, or both; (2) when plasma retinol levels are persistently low, and as the hepatic deposits of the xenobiotics build up, there are changes in the vitamin A pool size and composition of the liver. Candidate enzymes are retinyl ester hydrolase and cytochrome P450. The relationship between these two events will be studied in further detail.

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Vitamin A contained in the lipid droplets of rat liver stellate cells is substrate for acid retinyl ester hydrolase

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(95)00173-5 ◽

1995 ◽

Vol 1259 (3) ◽

pp. 271-276 ◽

Cited By ~ 15

Author(s):

Véronique Azaïs-Braesco ◽

Isabelle Dodeman ◽

Serge Delpal ◽

Marie-Cécile Alexandre-Gouabau ◽

Anne Partier ◽

...

Keyword(s):

Vitamin A ◽

Rat Liver ◽

Lipid Droplets ◽

Stellate Cells ◽

Retinyl Ester ◽

Ester Hydrolase ◽

Retinyl Ester Hydrolase

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Factors Influencing the Level and Interanimal Variability of Retinyl Ester Hydrolase Activity in Rat Liver

Journal of Nutrition ◽

10.1093/jn/117.12.2066 ◽

1987 ◽

Vol 117 (12) ◽

pp. 2066-2071 ◽

Cited By ~ 16

Author(s):

Dale A. Cooper ◽

Harold C. Furr ◽

James Allen Olson

Keyword(s):

Rat Liver ◽

Hydrolase Activity ◽

Retinyl Ester ◽

Ester Hydrolase ◽

Factors Influencing ◽

Retinyl Ester Hydrolase

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A comparative study on the effects of oral amiodarone and trimeprazine, two in vitro retinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

British Journal Of Nutrition ◽

10.1079/bjn20051495 ◽

2005 ◽

Vol 94 (5) ◽

pp. 675-683 ◽

Cited By ~ 1

Author(s):

Rainer Schindler ◽

Tanja Fielenbach ◽

Gerhard Rave

Keyword(s):

Vitamin A ◽

Tolerance Test ◽

Brown Norway ◽

Oral Drug ◽

Retinyl Ester ◽

Ester Hydrolase ◽

Retinyl Ester Hydrolase ◽

Pre Treatment ◽

Plasma Retinol

Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.

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