PMID- 23949303 OWN - NLM STAT- MEDLINE DCOM- 20140318 LR - 20211203 IS - 1573-904X (Electronic) IS - 0724-8741 (Print) IS - 0724-8741 (Linking) VI - 30 IP - 9 DP - 2013 Sep TI - Effect of caloric restriction and AMPK activation on hepatic nuclear receptor, biotransformation enzyme, and transporter expression in lean and obese mice. PG - 2232-47 LID - 10.1007/s11095-013-1140-2 [doi] AB - PURPOSE: Fatty liver alters liver transporter expression. Caloric restriction (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1 deacetylase activity in liver. This study evaluated whether CR and CR mimetics reversed obesity-induced transporter expression in liver and hepatocytes. METHODS: mRNA and protein expression was determined in adult lean (lean) and leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase activators, and gene expression was determined. RESULTS: CR decreased Oatp1a1, Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased Abcc2 mRNA OB livers, whereas protein expression increased in both genotypes. CR increased Abcc3 protein expression increased in OB livers. CR did not alter Abcc1, 4 and 5 mRNA expression in lean mice but decreased expression in livers of OB mice. CR increased Abcc4 protein in lean, but not OB mice. CONCLUSIONS: CR restriction reversed the expression of some, but not all transporters in livers of OB mice. Overall, these data indicate a potential for CR to restore some hepatic transporter changes in OB mice, but suggest a functional leptin axis is needed for reversal of expression for some transporters. FAU - Kulkarni, Supriya R AU - Kulkarni SR AD - Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, 7 Greenhouse Road, Kingston, Rhode Island, 02881, USA. FAU - Xu, Jialin AU - Xu J FAU - Donepudi, Ajay C AU - Donepudi AC FAU - Wei, Wei AU - Wei W FAU - Slitt, Angela L AU - Slitt AL LA - eng GR - P20 GM103430/GM/NIGMS NIH HHS/United States GR - 5K22ES013782/ES/NIEHS NIH HHS/United States GR - K22 ES013782/ES/NIEHS NIH HHS/United States GR - R01 ES016042/ES/NIEHS NIH HHS/United States GR - P20RR016457/RR/NCRR NIH HHS/United States GR - P20 RR016457/RR/NCRR NIH HHS/United States GR - 4R01ES016042/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130816 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 11) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Abcb11 protein, mouse) RN - 0 (Lipids) RN - 0 (Liver-Specific Organic Anion Transporter 1) RN - 0 (Multidrug Resistance-Associated Protein 2) RN - 0 (Multidrug Resistance-Associated Proteins) RN - 0 (Oatp1a1 protein, mouse) RN - 0 (Organic Anion Transporters, Sodium-Independent) RN - 0 (Organic Cation Transport Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Slco1b2 protein, mouse) RN - 1YV0492L5Z (multidrug resistance-associated protein 3) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - ATP Binding Cassette Transporter, Subfamily B, Member 11 MH - ATP-Binding Cassette Transporters/genetics MH - Animals MH - Body Weight MH - *Caloric Restriction MH - Cells, Cultured MH - Enzyme Activation MH - *Gene Expression Regulation MH - Lipids/analysis MH - Liver/*metabolism/pathology MH - Liver-Specific Organic Anion Transporter 1 MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Multidrug Resistance-Associated Protein 2 MH - Multidrug Resistance-Associated Proteins/genetics MH - Obesity/*diet therapy/enzymology/*genetics/pathology MH - Organic Anion Transporters, Sodium-Independent/genetics MH - Organic Cation Transport Proteins/genetics MH - RNA, Messenger/genetics MH - Receptors, Cytoplasmic and Nuclear/genetics PMC - PMC4225720 MID - NIHMS516336 EDAT- 2013/08/21 06:00 MHDA- 2014/03/19 06:00 PMCR- 2014/11/10 CRDT- 2013/08/17 06:00 PHST- 2013/01/08 00:00 [received] PHST- 2013/07/01 00:00 [accepted] PHST- 2013/08/17 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] PHST- 2014/11/10 00:00 [pmc-release] AID - 10.1007/s11095-013-1140-2 [doi] PST - ppublish SO - Pharm Res. 2013 Sep;30(9):2232-47. doi: 10.1007/s11095-013-1140-2. Epub 2013 Aug 16.