Evidence for a role of developmental genes in the origin of obesity and body fat distribution.
Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and/or waist/hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.
Gesta
Stephane
S
Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA.
Blüher
Matthias
M
Yamamoto
Yuji
Y
Norris
Andrew W
AW
Berndt
Janin
J
Kralisch
Susan
S
Boucher
Jeremie
J
Lewis
Choy
C
Kahn
C Ronald
CR
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000254:growth & development* / Q000473:pathology; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D050218:Body Fat Distribution; D015992:Body Mass Index; D002454:Cell Differentiation; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D013045:Species Specificity; D020825:T-Box Domain Proteins / Q000235:genetics
C492044:GPC4 protein, human; D053673:Glypicans; C489213:HOXA5 protein, human; D019812:Heparan Sulfate Proteoglycans; D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; C114093:TBX15 protein, mouse