title: Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques.
abstract: Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model to examine the impact of a maternal Western-style diet (WSD) alone, or in combination with obesity (Ob/WSD), on fetal skeletal muscle metabolism studied in the early third trimester. We find that fetal muscle responds to Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and metabolic switches (CPT-1, PDK4) that promote lipid utilization over glucose oxidation. Ob/WSD fetuses also had reduced mitochondrial content, diminished oxidative capacity, and lower mitochondrial efficiency in muscle. The decrease in oxidative capacity and glucose metabolism was persistent in primary myotubes from Ob/WSD fetuses despite no additional lipid-induced stress. Switching obese mothers to a healthy diet prior to pregnancy did not improve fetal muscle mitochondrial function. Lastly, while maternal WSD alone led only to intermediary changes in fetal muscle metabolism, it was sufficient to increase oxidative damage and cellular stress. Our findings suggest that maternal obesity or WSD, alone or in combination, leads to programmed decreases in oxidative metabolism in offspring muscle. These alterations may have important implications for future health.
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, USA.|Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: McCurdy
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, California, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Schenk
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, USA.
authors.forename: Byron
authors.initials: B
authors.lastname: Hetrick
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Houck
authors.affiliation: David Geffen School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, University of California, Los Angeles, Los Angeles, California, USA.|Diabetes and Dyslipidaemia Laboratory, Baker IDI Heart and Diabetes Institute, Prahran, Victoria, Australia.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Drew
authors.affiliation: Departments of Health and Exercise Science and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Kaye
authors.affiliation: Departments of Health and Exercise Science and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lashbrook
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
authors.affiliation: Division of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Beaverton, Oregon, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Takahashi
authors.affiliation: Division of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Beaverton, Oregon, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Dean
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Nemkov
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Gertsman
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.affiliation: School of Sport Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Philp
authors.affiliation: David Geffen School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Hevener
authors.affiliation: Departments of Health and Exercise Science and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Chicco
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard
authors.affiliation: Division of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Beaverton, Oregon, USA.|Novo Nordisk Research Center, Seattle, Washington, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development; D005333:Fetus; D050356:Lipid Metabolism; D008251:Macaca; D039382:Maternal Nutritional Physiological Phenomena; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress; D011247:Pregnancy