title: Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism.
abstract: Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Simar
authors.forename: Karen
authors.initials: K
authors.lastname: Lambert
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001069:Appetite Regulation / Q000235:genetics / Q000502:physiology*; D004036:Diet, Atherogenic; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D044343:Overnutrition / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D005947:Glucose