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This version published online on July 21, 2005
Endocrinology, doi:10.1210/en.2005-0220
A more recent version of this article appeared on November 1, 2005
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Submitted on February 22, 2005
Accepted on July 14, 2005

Ob-Ra and ObRe are differentially expressed in adipose tissue in aged food restricted rats: Effects on circulating soluble leptin receptor levels

Nilda Gallardo, Carmen Arribas, Margarita Villar, Manuel Ros, José M. Carrascosa, Carmen Martínez, and Antonio Andres*

Área de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha. 13071 Ciudad Real, Spain; Facultad de Ciencias del Medio Ambiente, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha. 45071 Toledo, Spain; Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, 28922 Madrid, Spain; Centro de Biología Molecular "Severo Ochoa" UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain

* To whom correspondence should be addressed. E-mail: antonio.andres{at}uclm.es.

In rodents, soluble leptin receptor (SLR) may be generated by alternative splicing of ObR mRNA and/or as a cleavage product of ObR membrane-anchored receptors. In this study, we investigated the contribution of both processes on the generation of SLR in 3-, 8- and 24-month old Wistar rats fed ad libitum or under food restriction. To this end, we determined serum SLR levels, and analyzed ObRa and ObRe mRNA expression under these physiological conditions. Additionally, we studied the cellular distribution of ObRa and the generation of SLR by N-ethylmaleimide induced shedding from ObRa membrane receptors in isolated adipocytes. Serum SLR levels were significantly increased in 8- and 24-month old rats under food restriction, whereas similar amounts were found in rats of different ages fed ad libitum. ObRa and ObRe mRNA expression in epididymal adipose tissue increased with aging. In contrast, after food restriction ObRe mRNA expression decreased while ObRa mRNA expression further increased compared with 8- and 24-month old rats fed ad libitum. Additionally, food restriction promoted a change in the distribution of ObRa between internal and plasma membranes in isolated adipocytes, increasing its presence at the cell surface. Finally, the generation of SLR by N-ethylmaleimide induced shedding from ObRa was also increased under food restriction. These data suggest that shedding of ObRa membrane-anchored receptors, rather than ObRe expression, might preferentially contribute to the generation of the increased levels of soluble leptin receptor in serum under conditions of food restriction.
Key words: Leptin receptors • food restriction • aging • adipose tissue




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