title: Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.
abstract: Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport.
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.C.D., Q.C, A.L.S); Arizona Statistical Consulting Laboratory, The Bio5 Institute (Z.J.L.) and Department of Pharmacology and Toxicology, College of Pharmacy (N.J.C.), University of Arizona, Tucson, Arizona.
authors: Ajay C
authors: AC
authors: Donepudi
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.C.D., Q.C, A.L.S); Arizona Statistical Consulting Laboratory, The Bio5 Institute (Z.J.L.) and Department of Pharmacology and Toxicology, College of Pharmacy (N.J.C.), University of Arizona, Tucson, Arizona.
authors: Qiuqiong
authors: Q
authors: Cheng
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.C.D., Q.C, A.L.S); Arizona Statistical Consulting Laboratory, The Bio5 Institute (Z.J.L.) and Department of Pharmacology and Toxicology, College of Pharmacy (N.J.C.), University of Arizona, Tucson, Arizona.
authors: Zhenqiang James
authors: ZJ
authors: Lu
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.C.D., Q.C, A.L.S); Arizona Statistical Consulting Laboratory, The Bio5 Institute (Z.J.L.) and Department of Pharmacology and Toxicology, College of Pharmacy (N.J.C.), University of Arizona, Tucson, Arizona.
authors: Nathan J
authors: NJ
authors: Cherrington
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.C.D., Q.C, A.L.S); Arizona Statistical Consulting Laboratory, The Bio5 Institute (Z.J.L.) and Department of Pharmacology and Toxicology, College of Pharmacy (N.J.C.), University of Arizona, Tucson, Arizona aslitt@uri.edu.
authors: Angela L
authors: AL
authors: Slitt
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006728:Hormones / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010641:Phenotype; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D018528:ATP-Binding Cassette Transporters; D006728:Hormones; D014157:Transcription Factors