TY - JOUR
T1 - Agouti regulation of leptin expression in adipocytes
AU - Zemel, M. B.
AU - Jones, B.
AU - Moore, J. W.
AU - Kim, J. H.
AU - Wilkison, W. O.
AU - Moustaid, N.
N1 - Copyright:
Copyright 2006 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - Overexpression of the mouse agouti gene results in obesity. Humans express agouti in adipose tissue, and we have demonstrated that agouti protein stimulates lipogenesis in isolated human adipocytes. Since leptin (ob) is also expressed in human adipocytes, and other agents which stimulate lipogenesis, such as insulin, appear to increase leptin expression, we investigated the role of agouti in regulating leptin expression. Adipose tissue isolated from transgenic mice ubiquitously expressing agouti exhibited an approximately two-fold increase in leptin mRNA, and these mice exhibited a five-fold increase in circulating leptin (9.0±3 vs. 48.8±13.5 ng/mL, p<0.0005). To determine if this effect was specifically attributable to agouti or if it was secondary to the obesity exhibited by these animals, agouti cDNA was expressed in insect cells via a baculoviral expression vector to produce secreted agouti protein, which was then purified. Human adipocytes were then exposed to this agouti protein (50 nM) for 48 hours, and mRNA was isolated and probed for ob. Agouti exposure resulted in a 356% increase in ob mRNA levels compared to untreated cells (p<0.005). Thus, agouti specifically regulates ob expression; this stimulation may provide a mechanism to limit agouti-induced lipogenesis and obesity.
AB - Overexpression of the mouse agouti gene results in obesity. Humans express agouti in adipose tissue, and we have demonstrated that agouti protein stimulates lipogenesis in isolated human adipocytes. Since leptin (ob) is also expressed in human adipocytes, and other agents which stimulate lipogenesis, such as insulin, appear to increase leptin expression, we investigated the role of agouti in regulating leptin expression. Adipose tissue isolated from transgenic mice ubiquitously expressing agouti exhibited an approximately two-fold increase in leptin mRNA, and these mice exhibited a five-fold increase in circulating leptin (9.0±3 vs. 48.8±13.5 ng/mL, p<0.0005). To determine if this effect was specifically attributable to agouti or if it was secondary to the obesity exhibited by these animals, agouti cDNA was expressed in insect cells via a baculoviral expression vector to produce secreted agouti protein, which was then purified. Human adipocytes were then exposed to this agouti protein (50 nM) for 48 hours, and mRNA was isolated and probed for ob. Agouti exposure resulted in a 356% increase in ob mRNA levels compared to untreated cells (p<0.005). Thus, agouti specifically regulates ob expression; this stimulation may provide a mechanism to limit agouti-induced lipogenesis and obesity.
UR - http://www.scopus.com/inward/record.url?scp=3543071942&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:3543071942
VL - 11
SP - A352
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -