title: Modification of the fatty acid composition of an obesogenic diet improves the maternal and placental metabolic environment in obese pregnant mice.
abstract: Peri-conceptional exposure to maternal obesogenic nutrition is associated with in utero programming of later-life overweight and metabolic disease in the offspring. We aimed to investigate whether dietary intervention with a modified fatty acid quality in an obesogenic high-calorie (HC) diet during the preconception and gestational phases can improve unfavourable effects of an adipogenic maternal environment. In NMRI mice, peri-conceptional and gestational obesity was induced by feeding a HC diet (controls), and they were compared with dams on a fat-modified (Fat-mod) HC diet of the same energy content but enriched with medium-chain fatty acids (MCFAs) and adjusted to a decreased ratio of n-6 to n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). Effects on maternal and placental outcomes at delivery (day 17.5 post coitum) were investigated. Despite comparable energy assimilation between the two groups of dams, the altered fatty acid composition of the Fat-mod HC diet induced lower maternal body weight, weights of fat depots, adipocyte size, and hepatic fat accumulation compared to the unmodified HC diet group. Further, there was a trend towards lower fasting glucose, insulin and leptin concentrations in dams fed the Fat-mod HC diet. Phenotypic changes were accompanied by inhibition of transcript and protein expression of genes involved in hepatic de novo lipogenesis comprising PPARG2 and its target genes Fasn, Acaca, and Fabp4, whereas regulation of other lipogenic factors (Srebf1, Nr1h3, Abca1) appeared to be more complex. The modified diet led to a sex-specific placental response by upregulating PPARG-dependent fatty acid transport gene expression in female versus male placentae. Qualitative modification of the fatty acid spectrum of a high-energy maternal diet, using a combination of both MCFAs and n-3 LC-PUFAs, seems to be a promising interventional approach to ameliorate the adipogenic milieu of mice before and during gestation.
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Martina.Gimpfl@med.uni-muenchen.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Gimpfl
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: jan.rozman@helmholtz-muenchen.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. Electronic address: dahlhoff@lmb.uni-muenchen.de.
authors.forename: Maik
authors.initials: M
authors.lastname: Dahlhoff
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany; Molecular Nutritional Medicine, Else-Kröner Fresenius Center, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising, Germany. Electronic address: raphaela.kuebeck@tum.de.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Kübeck
authors.affiliation: Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Veterinärstrasse 13, 80539 Munich, Germany. Electronic address: blutke@patho.vetmed.uni-muenchen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Blutke
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. Electronic address: birgit.rathkolb@helmholtz-muenchen.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: Molecular Nutritional Medicine, Else-Kröner Fresenius Center, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising, Germany. Electronic address: mk@tum.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany. Electronic address: hrabe@helmholtz-muenchen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Soner.Oener-Sieben@med.uni-duesseldorf.de.
authors.forename: Soner
authors.initials: S
authors.lastname: Öner-Sieben
authors.affiliation: Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Seibt@med.uni-duesseldorf.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Seibt
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Adelbert.Roscher@med.uni-muenchen.de.
authors.forename: Adelbert A
authors.initials: AA
authors.lastname: Roscher
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. Electronic address: ewolf@lmb.uni-muenchen.de.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany; Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: regina.ensenauer@med.uni-duesseldorf.de.
authors.forename: Regina
authors.initials: R
authors.lastname: Ensenauer
mesh_terms: D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011257:Pregnancy Proteins / Q000096:biosynthesis*
chemical_list: D005231:Fatty Acids, Unsaturated; D011257:Pregnancy Proteins
keywords: Medium-chain fatty acids; Nutrition; Obesity; Placenta; Pregnancy; n-3 fatty acids