title: Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring.
abstract: Maternal obesity and overconsumption of saturated fats during pregnancy have profound effects on offspring health, ranging from metabolic to behavioral disorders in later life. The influence of high-fat diet (HFD) exposure on the development of brain regions implicated in anxiety behavior is not well understood. We previously found that maternal HFD exposure is associated with an increase in anxiety behavior and alterations in the expression of several genes involved in inflammation via the glucocorticoid signaling pathway in adult rat offspring. During adolescence, the maturation of feedback systems mediating corticosteroid sensitivity is incomplete, and therefore distinct from adulthood. In this study, we examined the influence of maternal HFD on several measures of anxiety behavior and gene expression in adolescent offspring. We examined the expression of corticosteroid receptors and related inflammatory processes, as corticosteroid receptors are known to regulate circulating corticosterone levels during basal and stress conditions in addition to influencing inflammatory processes in the hippocampus and amygdala. We found that adolescent animals perinatally exposed to HFD generally showed decreased anxiety behavior accompanied by a selective alteration in the expression of the glucocorticoid receptor and several downstream inflammatory genes in the hippocampus and amygdala. These data suggest that adolescence constitutes an additional period when the effects of developmental programming may modify mental health trajectories.
authors.affiliation: Centre for Environmental Epigenetics and Development, Department of Biological Sciences, University of Toronto, Room SW548, Scarborough Campus, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Centre for Environmental Epigenetics and Development, Department of Biological Sciences, University of Toronto, Room SW548, Scarborough Campus, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: W
authors.initials: W
authors.lastname: de Vega
authors.affiliation: Centre for Environmental Epigenetics and Development, Department of Biological Sciences, University of Toronto, Room SW548, Scarborough Campus, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Sivanathan
authors.affiliation: Centre for Environmental Epigenetics and Development, Department of Biological Sciences, University of Toronto, Room SW548, Scarborough Campus, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: S
authors.initials: S
authors.lastname: St-Cyr
authors.affiliation: Centre for Environmental Epigenetics and Development, Department of Biological Sciences, University of Toronto, Room SW548, Scarborough Campus, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. Electronic address: patrick.mcgowan@utoronto.ca.
authors.forename: P O
authors.initials: PO
authors.lastname: McGowan
mesh_terms: D000375:Aging; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal; D003345:Corticosterone / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003345:Corticosterone
keywords: anxiety behavior; gene expression programming; glucocorticoid receptor; inflammatory; maternal; obesity