title: Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN).
abstract: Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p<0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p<0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p<0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School, F3970 Mott Children's Hospital, Ann Arbor, MI 48109-0245, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tazuke
authors.forename: Robert A
authors.initials: RA
authors.lastname: Drongowski
authors.forename: Imad
authors.initials: I
authors.lastname: Btaiche
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D008055:Lipids / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor