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Am J Physiol Regul Integr Comp Physiol (February 24, 2005). doi:10.1152/ajpregu.00858.2004
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Submitted on December 21, 2004
Accepted on February 22, 2005

Sympathetic Denervation Does Not Prevent a Reduction in Fat Pad Size of Rats or Mice Treated with Peripherally Administered Leptin

Cherie R Rooks1, Dawn M Penn1, Emily E Kelso1, Robert R Bowers2, Timothy J Bartness2, and Ruth B. S Harris1*

1 Department of Foods and Nutrition, University of Georgia, Athens, GA, USA
2 Department of Biology and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: harrisrb{at}uga.edu.

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In Experiment 1 one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine in C57BL/6 mice which were then infused for 13 days with PBS or 10 ug leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and non-injected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague Dawley rats that were infused with 50 ug leptin/day. Leptin had little effect on EPI weight or NE content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content, but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.




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