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

Abstract

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 [13 C]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). [13 C]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 [ 13 C]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 [13 C]palmitate concentrations allowed complete discrimination between normal (> 92%) and reduced (< 92%) fat absorption, whereas the percentage absorption of [ 13 C]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 [13 C]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

Laxative Treatment With Polyethylene Glycol Does Not Affect Lipid Absorption in Rats

“…To further investigate fat uptake, we studied plasma appearance of 13 C-labeled fats, derived from intragastrically administered 13 C-labeled FFA or triglycerides (16). We found absorption kinetics to be comparable in PEG-treated versus baseline conditions.…”

Functional Development of Fat Absorption in Term and Preterm Neonates Strongly Correlates with Ability to Absorb Long-Chain Fatty Acids from Intestinal Lumen

“…The time point of the serum sampling, namely 4 h after administration, was arbitrarily chosen, partly based on 13 C-PA experiments in an animal model (29) and on a […”

“…A theoretical alternative for the use of plasma values would have been the quantitation of the unabsorbed 13 C-fatty acids in the feces. However, the correlation between unabsorbed (fecal) concentrations of 13 C-fatty acids and dietary fat absorption has been demonstrated to be weak, probably attributable to tracer effects and to compensatory 13 C-fatty acid absorption in the distal parts of the small intestine (29,39,(41)(42)(43)(44).…”

“…At 4 h after administration, a blood sample was taken to analyze serum concentrations of the specific 13 C-lipids. The time 4 h was chosen based on rat studies in which plasma concentrations of 13 C-lipids were stable between 1 and 5 h after their intraduodenal administration (29).…”

Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption

“…Mice were housed in metabolic cages for 48 h. Mice were allowed to acclimate to the new environment for 24 h before data and sample collection. Body weight, food intake, water intake, and urine output were measured during the subsequent 24 h. Urine and feces samples were collected over 24 h. Acid steatocrit was measured as described previously, and daily fat absorption was calculated as previously described (20,42). For the analysis of energy expenditure, indirect calorimetry and physical activity were measured using the Labmaster system (TSE Systems, Bad Homburg, Germany) as previously described (22,36).…”