Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 102 (50): 18011-18016

Copyright © 2005 by the National Academy of Sciences.

Fat storage in adipocytes requires inactivation of leptin's paracrine activity: Implications for treatment of human obesity

May-yun Wang *, Lelio Orci {dagger}, Mariella Ravazzola {dagger}, and Roger H. Unger *, {ddagger}, §

*Gifford Laboratories, Touchstone Center for Diabetes Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8854; {ddagger}Veterans Affairs Medical Center, Dallas, TX 75216; and {dagger}Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 Geneva 4, Switzerland



View larger version (20K):

[in a new window]
 
Fig. 1.. Effect of high fat feeding on body weight and plasma leptin levels. (A) Mean (±SEM) body weight of normal 5-week-old SD rats fed a 4% ({triangleup}) or 60% ({bullet}) fat diet for the times as indicated. (B) Mean (±SEM) plasma leptin level of 4% and 60% fat-fed rats. (C) Phosphorylated STAT-3 content of WAT of the rats 12 weeks after the start of the 4% or 60% fat feeding.

 


View larger version (52K):

[in a new window]
 
Fig. 2.. Comparison of the effect of overnutrition on the response of adipose tissue to exogenous hyperleptinemia induced by i.v. administration of AdCMV-leptin (+) or AdCMV-{beta}-galactosidase as a control (–). (A) Mean (±SEM) plasma leptin levels. (B) Mean (±SEM) body fat, measured by magnetic nuclear resonance spectroscopy. (C) Phosphorylated and total STAT-3 content, measured by immunoblotting, of WAT in normal (+/+) ZDF rats fed either 6% or 60% fat.

 


View larger version (14K):

[in a new window]
 
Fig. 3.. Effect of 20 weeks of overnutrition on the expression profiles of leptin, the leptin inhibitor, SOCS-3, and the leptin receptor, Lepr-b, in adipose tissue of normal rats. (A) The mRNA of leptin. (B) Lepr-b. (C) SOCS-3 in WAT of normal lean SD rats fed either a 4% ({triangleup}) or 60% ({bullet}) fat diet (*, P < 0.05).

 


View larger version (47K):

[in a new window]
 
Fig. 4.. The adipocyte-specific Lepr-b transgene and its obesity-preventing phenotype. (A) Map of the aP2-Lepr-b transgene construct. (B) Immunoblot for Lepr-b in WAT from Lepr-b-transgenic mice and wild-type controls. (C) Mean (±SEM) body weight of Lepr-b-transgenic mice ({triangleup}) and wild-type controls ({bullet}) on a 60% fat diet. *, P < 0.001. (D) Gross appearance of a wild-type (Left) and a Lepr-b-transgenic (Right) mouse after 12 weeks on a 60% fat diet. (E) Comparison of WAT of a wild-type and a Lepr-b-transgenic mouse after 12 weeks on a 60% fat diet. (F) Activated STAT-3 (P-STAT-3) in WAT of wild-type and Lepr-b-transgenic mice on a 60% fat diet. (G) Activated AMP-activated protein kinase (P-AMPK) in WAT of the wild-type and Lepr-b-transgenic mice on a 60% fat diet.

 


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882