title: Hepatic gene expression in morbidly obese women: implications for disease susceptibility.
abstract: The objective of this study was to determine the molecular bases of disordered hepatic function and disease susceptibility in obesity. We compared global gene expression in liver biopsies from morbidly obese (MO) women undergoing gastric bypass (GBP) surgery with that of women undergoing ventral hernia repair who had experienced massive weight loss (MWL) following prior GBP. Metabolic and hormonal profiles were examined in MO vs. MWL groups. Additionally, we analyzed individual profiles of hepatic gene expression in liver biopsy specimens obtained from MO and MWL subjects. All patients underwent preoperative metabolic profiling. RNAs were extracted from wedge biopsies of livers from MO and MWL subjects, and analysis of mRNA expression was carried out using Affymetrix HG-U133A microarray gene chips. Genes exhibiting greater than twofold differential expression between MO and MWL subjects were organized according to gene ontology and hierarchical clustering, and expression of key genes exhibiting differential regulation was quantified by real-time-polymerase chain reaction (RT-PCR). We discovered 154 genes to be differentially expressed in livers of MWL and MO subjects. A total of 28 candidate disease susceptibility genes were identified that encoded proteins regulating lipid and energy homeostasis (PLIN, ENO3, ELOVL2, APOF, LEPR, IGFBP1, DDIT4), signal transduction (MAP2K6, SOCS-2), postinflammatory tissue repair (HLA-DQB1, SPP1, P4HA1, LUM), bile acid transport (SULT2A, ABCB11), and metabolism of xenobiotics (GSTT2, CYP1A1). Using gene expression profiling, we have identified novel candidate disease susceptibility genes whose expression is altered in livers of MO subjects. The significance of altered expression of these genes to obesity-related disease is discussed.
authors.affiliation: Department of Medicine and Research Service, Veterans Affairs Medical Center, Memphis, Tennessee, USA. melam@utmem.edu
authors.forename: Marshall B
authors.initials: MB
authors.lastname: Elam
authors.forename: George S
authors.initials: GS
authors.lastname: Cowan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rooney
authors.forename: M Lloyd
authors.initials: ML
authors.lastname: Hiler
authors.forename: Chandrahasa R
authors.initials: CR
authors.lastname: Yellaturu
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.forename: George E
authors.initials: GE
authors.lastname: Howell
authors.forename: Edwards A
authors.initials: EA
authors.lastname: Park
authors.forename: Ivan C
authors.initials: IC
authors.lastname: Gerling
authors.forename: Divyan
authors.initials: D
authors.lastname: Patel
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Corton
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Cagen
authors.forename: Henry G
authors.initials: HG
authors.lastname: Wilcox
authors.forename: Malay
authors.initials: M
authors.lastname: Gandhi
authors.forename: Micheal H
authors.initials: MH
authors.lastname: Bahr
authors.forename: Micheal C
authors.initials: MC
authors.lastname: Allan
authors.forename: Linus A
authors.initials: LA
authors.lastname: Wodi
authors.forename: George A
authors.initials: GA
authors.lastname: Cook
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hughes
authors.forename: Rajendra
authors.initials: R
authors.lastname: Raghow
mesh_terms: D000328:Adult; D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012313:RNA