title: High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.
abstract: Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany Department of Endocrinology and Metabolic Diseases, Charité-University of Medicine, Berlin, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kruse
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany Department of Endocrinology and Metabolic Diseases, Charité-University of Medicine, Berlin, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Keyhani-Nejad
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany Department of Endocrinology and Metabolic Diseases, Charité-University of Medicine, Berlin, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Isken
authors.affiliation: German Center for Diabetes Research, Neuherberg, Germany Research Unit of Molecular Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nitz
authors.affiliation: Research Unit of Molecular Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kretschmer
authors.affiliation: Research Unit of Molecular Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Reischl
authors.affiliation: Institute of Epidemiology II, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: de las Heras Gala
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany Department of Endocrinology and Metabolic Diseases, Charité-University of Medicine, Berlin, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Osterhoff
authors.affiliation: German Center for Diabetes Research, Neuherberg, Germany Research Unit of Molecular Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany Department of Endocrinology and Metabolic Diseases, Charité-University of Medicine, Berlin, Germany German Center for Diabetes Research, Neuherberg, Germany afhp@dife.de.
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
mesh_terms: D000273:Adipose Tissue; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D059305:Diet, High-Fat; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism*; D007249:Inflammation; D007333:Insulin Resistance / Q000235:genetics*; D007774:Lactation; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor