title: Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.
abstract: Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex.
  
  
  
  Male and female CRF-OE mice and WT littermates (4-6 months old) fedad libitumor overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals.
  
  
  
  Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females.
  
  
  
  These data indicate that CRF-OE mice have abnormal basal and fasting circulating hormones and hypothalamic feeding-related signals. CRF-OE also abolishes the sex difference in body weight, abdominal fat, and fasting-induced feeding and changes in plasma levels of leptin and acyl ghrelin.
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, David Geffen School of Medicine, University of California at Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California USA.
authors.forename: Lixin
authors.identifier: 0000-0001-8140-6325
authors.initials: L
authors.lastname: Wang
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, David Geffen School of Medicine, University of California at Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California USA ; Present address: Department for Internal Medicine, Martin-Luther-Krankenhaus, Caspar-Theyß-Str. 27-31, 14193 Berlin, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel-Stengel
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, David Geffen School of Medicine, University of California at Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California USA.
authors.forename: Pu-Qing
authors.initials: PQ
authors.lastname: Yuan
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, David Geffen School of Medicine, University of California at Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California USA ; Present address: Department for Psychosomatic Medicine, Charité Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, David Geffen School of Medicine, University of California at Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004435:Eating; D005215:Fasting / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D050152:Intra-Abdominal Fat; D008297:Male; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D001786:Blood Glucose; C101531:CRF receptor type 2; D009478:Neuropeptide Y; D036361:Peptide Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Adrenals; CRF-overexpressing mice; Corticosterone; Fasting; Ghrelin; Glucose; Hypothalamic neuropeptide Y; Insulin; Leptin; Sex difference; Visceral fat