Submitted on February 28, 2007
Accepted on June 6, 2007
Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria
Karin E. R Gooijert1, Rick Havinga2, Alida R Oosterloo-Duinkerken3, Enge E.A. Venekamp-Hoolsema4, Folkert Kuipers5, and Henkjan J. Verkade6*
1 Center of Liver, Digestive and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, Groningen, Netherlands
2 Center for Liver, Digestive and Metabolic Disease, Laboratory of Pediatrics, University Center Groningen, Groningen, groningen, Netherlands
3 Laboratory Center, University Medical Center Groningen, Groningen, Netherlands
4 Laboratory Center, University Medical Center Groningen, Groningen, groningen, Netherlands
5 Laboratory of Pediatrics, University Medical Center Groningen, Center for Liver, Digestive and Metabolic Disease, 9713 EZ Groningen, United States
6 Center for liver, digestive and metabolic diseases, Laboratory of Pediatrics, University Medical Center Groningen, Groningen, Netherlands
* To whom correspondence should be addressed. E-mail: h.j.verkade{at}med.umcg.nl.
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 have investigated whether stimulation of fecal fat excretion enhance the disposal of PP in fch/fch mice. Fch/fch mice were fed for eight weeks with a high-fat diet (16 wt% fat; control), or with the high-fat diet mixed with either a non-absorbable 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 six fold of control values. However, none of the different treatments have affected fecal PP excretion or hepatic PP concentration. Treatment of fch/fch mice with a high-fat diet, a non-absorbable fat or orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. Present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.
