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Kruse, M.* ; Keyhani-Nejad, F.* ; Isken, F.* ; Nitz, B. ; Kretschmer, A. ; Reischl, E. ; de Las Heras Gala, T. ; Osterhoff, M.A.* ; Grallert, H. ; Pfeiffer, A.F.*

A high fat diet during mouse pregnancy and lactation targets GIP-regulated metabolic pathways in adult male offspring.

Diabetes 65, 574-584 (2016)
Publ. Version/Full Text Postprint Research data DOI
Open Access Green
Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the Gastric Inhibitory Polypeptide Receptor (GIPR) prevents high fat diet 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 high fat diet (HFD) during pregnancy (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, obese, exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being re-introduced to HFD similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared to 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 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dependent Insulinotropic Polypeptide; Adipose-tissue; Induced Obesity; Mice; Glucose; Inhibition; Deficiency; Activation; Expression; Resistance
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 65, Issue: 3, Pages: 574-584 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed