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Am J Physiol Gastrointest Liver Physiol 293: G510-G516, 2007. First published June 28, 2007; doi:10.1152/ajpgi.00102.2007
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LIVER AND BILIARY TRACT

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Karin E. R. Gooijert, Rick Havinga, Alida R. Oosterloo-Duinkerken, Enge E. A. Venekamp-Hoolsema, Folkert Kuipers, and Henkjan J. Verkade

Pediatric Gastroenterology, Department of Pediatrics, Groningen University Institute for Drug Exploration, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands

Submitted 28 February 2007 ; accepted in final form 6 June 2007

Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient (fch/fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/fch mice. Fch/fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.

fch/fch mice; ferochelatase; nonabsorbable fat; sucrose polyesters


Address for reprint requests and other correspondence: H. J. Verkade, Centre for Liver, Digestive and Metabolic Diseases, Pediatric Gastroenterology, Dept. of Pediatrics, CMC IV, Rm. Y4.107a, Univ. Medical Centre Groningen, PO Box 30.001, Groningen 9700 RB, The Netherlands (e-mail: h.j.verkade{at}med.umcg.nl)






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