title: A Western-style obesogenic diet alters maternal metabolic physiology with consequences for fetal nutrient acquisition in mice.
abstract: In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy, although their effects on the metabolism of the mother, in relation to feto-placental glucose utilization and growth, are unknown. In the present study, the consumption of an obesogenic HFHS diet compromised maternal glucose tolerance and insulin sensitivity in late pregnancy in association with dysregulated lipid and glucose handling by the dam. These maternal metabolic changes induced by HFHS feeding were related to altered feto-placental glucose metabolism and growth. A HFHS diet during pregnancy therefore causes maternal metabolic dysfunction with consequences for maternal nutrient allocation for fetal growth. These findings have implications for the health of women and their infants, who consume obesogenic diets during pregnancy.
  
  
  
  In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy. However, the impacts of a HFHS diet during pregnancy on maternal insulin sensitivity and signalling in relation to feto-placental growth and glucose utilization are unknown. The present study examined the effects of a HFHS diet during mouse pregnancy on maternal glucose tolerance and insulin resistance, as well as, on feto-placental glucose metabolism. Female mice were fed a control or HFHS diet from day (D) 1 of pregnancy (term = D20.5). At D16 or D19, dams were assessed for body composition, metabolite and hormone concentrations, tissue abundance of growth and metabolic signalling pathways, glucose tolerance and utilization and insulin sensitivity. HFHS feeding perturbed maternal insulin sensitivity in late pregnancy; hepatic insulin sensitivity was higher, whereas sensitivity of the skeletal muscle and white adipose tissue was lower in HFHS than control dams. These changes were accompanied by increased adiposity and reduced glucose production and glucose tolerance of HFHS dams. The HFHS diet also disturbed the hormone and metabolite milieu and altered expression of growth and metabolic signalling pathways in maternal tissues. Furthermore, HFHS feeding was associated with impaired feto-placental glucose metabolism and growth. A HFHS diet during pregnancy therefore causes maternal metabolic dysfunction with consequences for maternal nutrient allocation for fetal growth. These findings have implications for the health of women and their infants, who consume HFHS diets during pregnancy.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Musial
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Owen R
authors.identifier: 0000-0001-7537-3264
authors.initials: OR
authors.lastname: Vaughan
authors.affiliation: University of Cambridge Metabolic Research Laboratories, and MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Denise S
authors.identifier: 0000-0003-2610-277X
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.affiliation: University of Cambridge Metabolic Research Laboratories, and MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Voshol
authors.affiliation: University of Cambridge Metabolic Research Laboratories, and MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Susan E
authors.identifier: 0000-0001-8753-5144
authors.initials: SE
authors.lastname: Ozanne
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Amanda N
authors.identifier: 0000-0002-4931-4233
authors.initials: AN
authors.lastname: Sferruzzi-Perri
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D066273:Diet, Western; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009035:Mothers; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
keywords: fetal growth; gestational diabetes; glucose metabolism; insulin resistance; nutrient partitioning; pregnancy