title: Agouti expression in human adipose tissue: functional consequences and increased expression in type 2 diabetes.
abstract: It is well recognized that the agouti/melanocortin system is an important regulator of body weight homeostasis. Given that agouti is expressed in human adipose tissue and that the ectopic expression of agouti in adipose tissue results in moderately obese mice, the link between agouti expression in human adipose tissue and obesity/type 2 diabetes was investigated. Although there was no apparent relationship between agouti mRNA levels and BMI, agouti mRNA levels were significantly elevated in subjects with type 2 diabetes. The regulation of agouti in cultured human adipocytes revealed that insulin did not regulate agouti mRNA, whereas dexamethasone treatment potently increased the levels of agouti mRNA. Experiments with cultured human preadipocytes and with cells obtained from transgenic mice that overexpress agouti demonstrated that melanocortin receptor (MCR) signaling in adipose tissue can regulate both preadipocyte proliferation and differentiation. Taken together, these results reveal that agouti can regulate adipogenesis at several levels and suggest that there are functional consequences of elevated agouti levels in human adipose tissue. The influence of MCR signaling on adipogenesis combined with the well-established role of MCR signaling in the hypothalamus suggest that adipogenesis is coordinately regulated with food intake and energy expenditure.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawronska-Kozak
authors.forename: Lenka
authors.initials: L
authors.lastname: Janderová
authors.forename: Taylor
authors.initials: T
authors.lastname: Nguyen
authors.forename: Angela
authors.initials: A
authors.lastname: Murrell
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Stephens
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D054366:Agouti Signaling Protein; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000378:metabolism; D044101:Receptors, Melanocortin; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
chemical_list: D054366:Agouti Signaling Protein; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor; D003907:Dexamethasone