title: The effects of high fat diet on the basal activity of the hypothalamus-pituitary-adrenal axis in mice.
abstract: Alterations in hypothalamus-pituitary-adrenal (HPA) axis activity have been linked to the development of the metabolic syndrome (MetS). Common features of the MetS, like insulin resistance and obesity, are reproducibly induced by high fat diet (HFD) in animal models of diet-induced obesity. These models, hampered by methodological differences, reveal conflicting results with respect to HPA axis activation. This study was aimed to evaluate in detail nonstressed diurnal HPA axis activity in mice during obesity development. Male C57Bl/6J mice were fed high or low fat diet for 12 weeks. HPA axis activity was evaluated by plasma corticosterone concentrations (at 0700, 1200, and 1800  h), corticotropin-releasing hormone (CRH), and glucocorticoid receptor (GR) mRNA expression in the hippocampus, amygdala, and hypothalamus, and 11β-hydroxysteroid dehydrogenase type-1 and -2 (11β-HSD-1 and -2) expression in adipose tissue and liver. Within 1 week, the HFD induced obesity and decreased corticosterone levels at 1200 and 1800  h, which persisted throughout the experiment. Twelve weeks of HFD decreased CRH mRNA in the paraventricular nucleus (PVN) and amygdala and GR mRNA in the PVN at 0900  h. At 1800  h, CRH mRNA expression increased in the PVN and amygdala, and GR mRNA increased in the CA1 region. 11β-HSD-1 expressions decreased in gonadal, visceral, and subcutaneous adipose tissues at 0900 and 1800  h, whereas hepatic 11β-HSD-1 expression increased at 1800  h, whereas 11β-HSD-2 expression was unaffected. The HFD induces complex changes in the diurnal regulation of the different components of the HPA axis. These changes are not unequivocally characterized by increased, but rather by decreased HPA axis activity.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. h.e.auvinen@lumc.nl
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Auvinen
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone