Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated fasting response in the mouse - PubMed (original) (raw)
Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated fasting response in the mouse
Tineke Kok et al. Gastroenterology. 2003 Jan.
Abstract
Background & aims: Fatty acids are natural ligands of the peroxisome proliferator-activated receptor alpha (PPARalpha). Synthetic ligands of this nuclear receptor, i.e., fibrates, induce the hepatic expression of the multidrug resistance 2 gene (Mdr2), encoding the canalicular phospholipid translocator, and affect hepatobiliary lipid transport. We tested whether fasting-associated fatty acid release from adipose tissues alters hepatic transporter expression and bile formation in a PPARalpha-dependent manner.
Methods: A 24-hour fasting/48-hour refeeding schedule was used in wild-type and Pparalpha((-/-)) mice. Expression of genes involved in the control of bile formation was determined and related to secretion rates of biliary components.
Results: Expression of Pparalpha, farnesoid X receptor, and liver X receptor alpha genes encoding nuclear receptors that control hepatic bile salt and sterol metabolism was induced on fasting in wild-type mice only. The expression of Mdr2 was 5-fold increased in fasted wild-type mice and increased only marginally in Pparalpha((-/-)) mice, and it normalized on refeeding. Mdr2 protein levels and maximal biliary phospholipid secretion rates were clearly increased in fasted wild-type mice. Hepatic expression of the liver X receptor target genes ATP binding cassette transporter a1 (Abca1), Abcg5, and Abcg8, implicated in hepatobiliary cholesterol transport, was induced in fasted wild-type mice only. However, the maximal biliary cholesterol secretion rate was reduced by approximately 50%.
Conclusions: Induction of Mdr2 expression and function is part of the PPARalpha-mediated fasting response in mice. Fasting also induces expression of the putative hepatobiliary cholesterol transport genes Abca1, Abcg5, and Abcg8, but, nonetheless, maximal biliary cholesterol excretion is decreased after fasting.
Comment in
- Biliary lipid secretion, membrane pumps, and the metabolic response to fasting: distinct PPAR-ts of a common regulatory pathway.
Newberry EP, Davidson NO. Newberry EP, et al. Gastroenterology. 2003 Jan;124(1):254-7. doi: 10.1053/gast.2003.50029. Gastroenterology. 2003. PMID: 12512050 Review. No abstract available.
Similar articles
- Peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice.
Kok T, Bloks VW, Wolters H, Havinga R, Jansen PL, Staels B, Kuipers F. Kok T, et al. Biochem J. 2003 Feb 1;369(Pt 3):539-47. doi: 10.1042/BJ20020981. Biochem J. 2003. PMID: 12381268 Free PMC article. - Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice.
Plösch T, van der Veen JN, Havinga R, Huijkman NC, Bloks VW, Kuipers F. Plösch T, et al. Am J Physiol Gastrointest Liver Physiol. 2006 Sep;291(3):G414-23. doi: 10.1152/ajpgi.00557.2005. Epub 2006 Apr 13. Am J Physiol Gastrointest Liver Physiol. 2006. PMID: 16614371 - Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients.
Geuken E, Visser DS, Leuvenink HG, de Jong KP, Peeters PM, Slooff MJ, Kuipers F, Porte RJ. Geuken E, et al. Hepatology. 2005 Nov;42(5):1166-74. doi: 10.1002/hep.20886. Hepatology. 2005. PMID: 16250035 - Hepatic canalicular membrane 1: The role of mdr2 P-glycoprotein in hepatobiliary lipid transport.
Elferink RP, Tytgat GN, Groen AK. Elferink RP, et al. FASEB J. 1997 Jan;11(1):19-28. doi: 10.1096/fasebj.11.1.9034162. FASEB J. 1997. PMID: 9034162 Review. - Bile salt excretory pump: biology and pathobiology.
Suchy FJ, Ananthanarayanan M. Suchy FJ, et al. J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S10-6. doi: 10.1097/01.mpg.0000226385.71859.5f. J Pediatr Gastroenterol Nutr. 2006. PMID: 16819395 Review.
Cited by
- Fasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation.
Chasseigneaux S, Cochois-Guégan V, Lecorgne L, Lochus M, Nicolic S, Blugeon C, Jourdren L, Gomez-Zepeda D, Tenzer S, Sanquer S, Nivet-Antoine V, Menet MC, Laplanche JL, Declèves X, Cisternino S, Saubaméa B. Chasseigneaux S, et al. Fluids Barriers CNS. 2024 Apr 8;21(1):33. doi: 10.1186/s12987-024-00526-8. Fluids Barriers CNS. 2024. PMID: 38589879 Free PMC article. - Targeting fibrosis, mechanisms and cilinical trials.
Zhao M, Wang L, Wang M, Zhou S, Lu Y, Cui H, Racanelli AC, Zhang L, Ye T, Ding B, Zhang B, Yang J, Yao Y. Zhao M, et al. Signal Transduct Target Ther. 2022 Jun 30;7(1):206. doi: 10.1038/s41392-022-01070-3. Signal Transduct Target Ther. 2022. PMID: 35773269 Free PMC article. Review. - Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling.
Okyar A, Kumar SA, Filipski E, Piccolo E, Ozturk N, Xandri-Monje H, Pala Z, Abraham K, Gomes ARGJ, Orman MN, Li XM, Dallmann R, Lévi F, Ballesta A. Okyar A, et al. Sci Rep. 2019 Jul 19;9(1):10505. doi: 10.1038/s41598-019-46977-0. Sci Rep. 2019. PMID: 31324853 Free PMC article. - The Diurnal Timing of Starvation Differently Impacts Murine Hepatic Gene Expression and Lipid Metabolism - A Systems Biology Analysis Using Self-Organizing Maps.
Rennert C, Vlaic S, Marbach-Breitrück E, Thiel C, Sales S, Shevchenko A, Gebhardt R, Matz-Soja M. Rennert C, et al. Front Physiol. 2018 Sep 10;9:1180. doi: 10.3389/fphys.2018.01180. eCollection 2018. Front Physiol. 2018. PMID: 30271348 Free PMC article. - Primary prevention of atherosclerosis by pretreatment of low-density lipoprotein receptor knockout mice with sesame oil and its aqueous components.
Aluganti Narasimhulu C, Burge KY, Doomra M, Riad A, Parthasarathy S. Aluganti Narasimhulu C, et al. Sci Rep. 2018 Aug 16;8(1):12270. doi: 10.1038/s41598-018-29849-x. Sci Rep. 2018. PMID: 30115989 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases