title: Central mechanisms of adiposity in adult female mice with androgen excess.
abstract: OBJECTIVE
  Androgen excess in women is associated with visceral adiposity. However, little is known on the mechanism through which androgen promotes visceral fat accumulation.
  
  
  METHODS
  To address this issue, female mice to chronic androgen excess using 5α-dihydrotestosterone (DHT) and studied the regulation of energy homeostasis was exposed.
  
  
  RESULTS
  DHT induced a leptin failure to decrease body weight associated with visceral adiposity but without alterations in leptin anorectic action. This paralleled leptin's failure to upregulate brown adipose tissue expression of uncoupling protein-1, associated with decreased energy expenditure (EE). DHT decreased hypothalamic proopiomelanocortin (pomc) mRNA expression and increased POMC intensity in neuronal bodies of the arcuate nucleus while simultaneously decreasing the intensity of POMC projections to the dorsomedial hypothalamus (DMH). This was associated with a failure of the melanocortin 4 receptor agonist melanotan-II to suppress body weight.
  
  
  CONCLUSIONS
  Taken together, these data indicate that androgen excess promotes visceral adiposity with reduced POMC neuronal innervation in the DMH, reduced EE but without hyperphagia.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Comprehensive Center on Obesity, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Nohara
authors.forename: Amanda
authors.initials: A
authors.lastname: Laque
authors.forename: Camille
authors.initials: C
authors.lastname: Allard
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000502:physiology*; D000728:Androgens / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D013196:Dihydrotestosterone / Q000008:administration & dosage* / Q000097:blood*; D004734:Energy Metabolism; D005260:Female; D006963:Hyperphagia / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000728:Androgens; D007473:Ion Channels; D020738:Leptin; C574273:MC4R protein, mouse; D024101:Mitochondrial Proteins; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D013196:Dihydrotestosterone; C079282:melanotan-II; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin