title: Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice.
abstract: The gynecological disease endometriosis is characterized by the deposition and proliferation of endometrial cells outside the uterus and clinically is linked to low body mass index (BMI). Gene expression in the liver of these women has not been reported. We hypothesized that endometriosis may impact hepatic gene expression, promoting a low BMI. To determine the effect of endometriosis on liver gene expression, we induced endometriosis in female mice by suturing donor mouse endometrium into the peritoneal cavity and measuring the weight of these mice. Dual-energy X-ray absorptiometry (DEXA) scanning of these mice showed lower body weight and lower total body fat than controls. Microarray analysis identified 26 genes differentially regulated in the livers of mice with endometriosis. Six of 26 genes were involved in metabolism. Four of six genes were upregulated and were related to weight loss, whereas two genes were downregulated and linked to obesity. Expression levels of Cyp2r1, Fabp4, Mrc1, and Rock2 were increased, whereas Igfbp1 and Mmd2 expression levels were decreased. Lep and Pparg, key metabolic genes in the pathways of the six genes identified from the microarray, were also upregulated. This dysregulation was specific to metabolic pathways. Here we demonstrate that endometriosis causes reduced body weight and body fat and disrupts expression of liver genes. We suggest that altered metabolism mediated by the liver contributes to the clinically observed low BMI that is characteristic of women with endometriosis. These findings reveal the systemic and multiorgan nature of endometriosis.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Teddy G
authors.initials: TG
authors.lastname: Goetz
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut ramana.mamillapalli@yale.edu.
authors.forename: Ramanaiah
authors.initials: R
authors.lastname: Mamillapalli
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010532:Peritoneal Diseases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C569548:Cyp2r1 protein, mouse; D053493:Cholestanetriol 26-Monooxygenase; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases
keywords: endometriosis; gene expression; liver; metabolism