Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Abstract

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 depotspecific 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 and͞or waist͞hip 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.adipose tissue ͉ gene expression ͉ subcutaneous ͉ intraabdominal

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

“…Striking was the 36-fold higher expression of the mesodermal developmental gene Tbx15 in visceral versus s.c. fat of lean humans. In visceral fat, Tbx15 expression was tightly inversely correlated with BMI and central fat distribution, as measured by WHR (11). In rodents, Tbx15 was also differentially distributed among depots, with levels in s.c. interscapular WAT > brown adipose tissue ∼ (equivalent) s.c. flank WAT ∼ perirenal WAT > intraabdominal epididymal WAT ∼ intraabdominal mesenteric WAT (20).…”

“…We previously reported differential expression of developmental genes in intraabdominal versus s.c. adipose depots in both humans and rodents and postulated that they may play a role in the control of differential adipocyte development and function between depots (1,11). Striking was the 36-fold higher expression of the mesodermal developmental gene Tbx15 in visceral versus s.c. fat of lean humans.…”

“…Recently, we and others have shown that several developmental genes, including several Hox genes, Shox2, Engrailed-1, and Tbx15, are differentially expressed between intraabdominal and s.c. adipocytes and preadipocytes of rodents and humans, in many cases by several orders of magnitude (9)(10)(11)(12). We hypothesized that these genes may play a role in adipose depot development and ultimately in differential adipose depot function.…”

“…We hypothesized that these genes may play a role in adipose depot development and ultimately in differential adipose depot function. In humans, three of these developmental genes exhibit relationships with BMI and WHR (11). One of the genes that exhibits a large interdepot difference in expression, and whose expression closely correlates with the level of obesity and pattern of fat distribution, is the developmental transcription factor T-box 15 (Tbx15) (11).…”

Fat poetry: a kingdom for PPARγ

“…Each of them has a different metabolic activity reflected in a different sensitivity to insulin [4,14,15]. Different expression profiles in sc and vis WAT of several genes involved in embryonic development and pattern specification suggest different genetically determined developmental programs in preadipocytes for the formation of each depot with its specific functional characteristics [16]. In addition to the main sc and vis depots, WAT is found in small amounts around other organs, such as the heart, kidney and genitalia.…”