Ageing increases SOCS-3 expression in rat hypothalamus: effects of food restriction

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Abstract

Aged Wistar rats are characterized by leptin and insulin resistance. The expression of SOCS-3 in hypothalamus increases with ageing. Food restriction during 3 months decreases obesity Lee index in aged rats with respect to their ad libitum aged-mates and brings serum leptin concentrations to values close to those of young rats. Food restriction partially reverts the increases in SOCS-3 mRNA levels associated with ageing. These results suggest that SOCS-3 may be a mediator of hypothalamic leptin resistance in the aged Wistar rat and that the hyperleptinemia associated with ageing is, at least in part, responsible for the increase of SOCS-3 expression in hypothalamus.

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Materials and methods

Animals. Wistar albino male rats aged 3, 7, and 23 months were used throughout the study. The animals were obtained from the “Centro de Biologı́a Molecular Severo Ochoa” (Madrid, Spain). Rats were housed individually in climate-controlled quarters with 12 h light cycle and handled following the European Union laws and NIH guidelines. Animals were fed standard laboratory chow. Special care was taken to minimize animal suffering and to reduce the number of animals used.

Food restriction. Four- and

Results and discussion

In agreement with previous results [6], Table 1 shows that body weight increases in Wistar rats with ageing without significant changes in obesity Lee index. Aged rats remain normoglycemic but exhibit a progressive and marked increase in plasma leptin concentrations. Food restriction during 3 months keeps body weight to about 75–80% of ad libitum fed aged-mates and elicits a significant decrease of obesity Lee index in 7- and 23-month-old rats. Additionally, food restriction brings plasma

Acknowledgements

S.P. and N.G. were supported by Grant 1FD1997-1754-C03-02. Financial aid from Quı́mica Farmacéutica Bayer (Spain) is acknowledged. The Centro de Biologı́a Molecular is the recipient of institutional aid from the Ramon Areces Foundation. This work was supported by Grants 1/2FD1997-1754-C03 and PIGE-02-17 from MCYT and URJC, respectively (Spain).

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