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ObRa and ObRe Are Differentially Expressed in Adipose Tissue in Aged Food-Restricted Rats: Effects on Circulating Soluble Leptin Receptor Levels

Área de Bioquímica, Facultad de Químicas (N.G., M.V., C.M., A.A.), Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain; Facultad de Ciencias del Medio Ambiente (C.A.), Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, 45071 Toledo, Spain; Facultad de Ciencias de la Salud (M.R.), Universidad Rey Juan Carlos, Alcorcón, 28922 Madrid, Spain; and Centro de Biología Molecular Severo Ochoa Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas (J.M.C.), Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain

Address all correspondence and requests for reprints to: Antonio Andrés, Área de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avenida Camilo José Cela, 10, 13071 Ciudad Real, Spain. 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 (AL) or under food restriction (FR). 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-ethyl-maleimide-induced shedding from ObRa membrane receptors in isolated adipocytes. Serum SLR levels were significantly increased in 8- and 24-month-old rats under FR, whereas similar amounts were found in rats of different ages fed AL. ObRa and ObRe mRNA expression in epididymal adipose tissue increased with aging. In contrast, after FR, ObRe mRNA expression decreased, whereas ObRa mRNA expression further increased compared with 8- and 24-month-old rats fed AL. Additionally, FR 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-ethyl-maleimide-induced shedding from ObRa was also increased under FR. 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 SLR in serum under conditions of FR.

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