| Alteration of hepatic but not renal transporter expression in diet-induced obese mice. | |
| | |
MedLine Citation:
|
PMID: 21430232 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Drug pharmacokinetics can be altered in obese and diabetic subjects. In consideration of the prevalence of obesity and diabetes, characterization of transporter expression in mouse models of diabetes and obesity may be a useful tool to aid in prediction of altered drug pharmacokinetics or adverse drug reactions. It has been reported that ob/ob mice, which display a severe obesity and diabetes phenotype, exhibit multiple changes in drug transporter expression in liver and kidney. In the present study, the mRNA and protein expression of major drug transporters was determined in livers and kidneys of diet-induced obese (DIO) C57BL/6J male mice. The mice were fed a high-fat diet (HFD) (60% fat) from 6 weeks of age and display obesity, fatty liver, and mild hyperglycemia. The HFD diet increased expression of multidrug resistance-associated proteins Abcc3 and 4 mRNA and protein in liver by 3.4- and 1.4-fold, respectively, compared with that detected in control mice fed a low-fat diet (LFD). In contrast, Abcc1 mRNA and protein decreased by 50% in livers of DIO mice compared with those in livers to lean mice. The HFD did not alter transporter expression in kidney compared with the LFD. In summary, unlike ob/ob and db/db mice, DIO mice exhibited a selective induction of efflux transporter expression in liver (i.e., Abcc3 and 4). In addition, diet-induced obesity affects transporter expression in liver but not kidney in the C57BL/6J mouse model. These data indicate that hepatic transporter expression is only slightly altered in a model of mild diabetes and nonalcoholic fatty liver disease and obesity. |
| | |
Authors:
|
Vijay R More; Angela L Slitt |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-23 |
Journal Detail:
|
Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 39 ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2011 Jun |
Date Detail:
|
Created Date: 2011-05-17 Completed Date: 2011-09-12 Revised Date: 2011-12-13 |
Medline Journal Info:
|
Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
|
Languages: eng Pagination: 992-9 Citation Subset: IM |
Affiliation:
|
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Body Weight Cytokines / biosynthesis, immunology Dietary Fats / administration & dosage* Disease Models, Animal Fatty Liver / metabolism Humans Kidney / immunology, metabolism* Liver / immunology, metabolism* Male Mice Mice, Inbred C57BL Obesity / metabolism* Organ Size Organic Anion Transporters / biosynthesis* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
|
1R01-ES016042/ES/NIEHS NIH HHS; 5K22-ES013782/ES/NIEHS NIH HHS; K22 ES013782-03/ES/NIEHS NIH HHS; R01 ES016042-01A1/ES/NIEHS NIH HHS; R01 ES016042-02/ES/NIEHS NIH HHS; R01 ES016042-03/ES/NIEHS NIH HHS; R01 ES016042-04/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 0/Dietary Fats; 0/Organic Anion Transporters |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: ROLE OF ISOVALERYL-CoA DEHYDROGENASE AND SHORT BRANCHED-CHAIN ACYL-CoA DEHYDROGENASE IN THE METABOLI...
Next Document: ABC transporter expression in human placenta as a function of pregnancy condition.