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Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption^1,2,3

¹ From the Centre for Liver, Digestive and Metabolic Diseases, Groningen Institute for Drug Studies, Academic Hospital Groningen, Groningen, Netherlands.

Background: Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids.

Objective: We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption.

Design: The absorption and appearance in plasma of [¹³C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [¹³C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance.

Results: Between 1 and 6 h after intraduodenal administration, plasma [¹³C]palmitate concentrations in control rats were 4–10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [¹³C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [¹³C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001).

Conclusions: The [¹³C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [¹³C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Key Words: Isotope labeling • stable isotopes • absorption • dietary fat metabolism • malabsorption syndromes • bile • enterohepatic circulation • bile salts • rats • bile deficiency

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