Esther Prince1, Farrah B Lazare2, William R Treem3, Jiliu Xu1, Jahangir Iqbal4, Xiaoyue Pan4, Joby Josekutty4, Meghan Walsh4, Virginia Anderson5, M Mahmood Hussain4, Steven M Schwarz6. 1. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, New York. 2. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, New York Department of Pediatrics, Winthrop University Medical Center, Mineola, New York. 3. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, New York Johnson & Johnson Pharmaceutical Research and Development, LLC, Titusville, New Jersey. 4. Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York. 5. Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, New York. 6. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, New York steven.schwarz@downstate.edu.
Abstract
OBJECTIVES: ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. METHODS: 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. RESULTS: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. CONCLUSIONS: PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways.
OBJECTIVES: ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. METHODS: 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. RESULTS: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. CONCLUSIONS:PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways.
Authors: M Skouroliakou; D Konstantinou; K Koutri; C Kakavelaki; M Stathopoulou; M Antoniadi; N Xemelidis; V Kona; S Markantonis Journal: Eur J Clin Nutr Date: 2010-06-16 Impact factor: 4.016
Authors: Caroline Améen; Ulrika Edvardsson; Anna Ljungberg; Lennart Asp; Peter Akerblad; Anna Tuneld; Sven-Olof Olofsson; Daniel Lindén; Jan Oscarsson Journal: J Biol Chem Date: 2004-11-09 Impact factor: 5.157
Authors: Gabriela S de Castro; João Felipe R Cardoso; Philip C Calder; Alceu A Jordão; Helio Vannucchi Journal: Nutrients Date: 2015-03-05 Impact factor: 5.717
Authors: Maria B Badia-Tahull; Elisabet Leiva-Badosa; Ramon Jodar-Masanes; Josep Maria Ramon-Torrell; Josep Llop-Talaveron Journal: Nutr J Date: 2015-07-02 Impact factor: 3.271
Authors: Mayara Áthina Reis; Rômulo Dias Novaes; Sueli Regina Baggio; André Luiz Machado Viana; Bruno Cesar Correa Salles; Stella Maris da Silveira Duarte; Maria Rita Rodrigues; Fernanda Borges de Araújo Paula Journal: Evid Based Complement Alternat Med Date: 2018-10-02 Impact factor: 2.629