Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC336
Effects of ghrelin administration on regulation of food intake in arthritic rats.
M. Lopez-Menduiña1, A. Martín1, E. Castillero1, A. Gómez-Sanmiguel1, A. López-Calderón1, M. Villanúa1
1. Physiology, Universidad Complutense, Madrid, Spain.
Adjuvant-induced arthritis is an animal model of chronic inflammation and rheumatoid arthritis. Arthritis induces cachexia that leads to loss of body weight, muscle atrophy and anorexia. Ghrelin is a circulating orexigenic hormone secreted from the gastrointestinal tract that is involved in the control of food intake and energy balance. Peripheral administration of exogenous ghrelin has been shown to increase food intake and body weight in rats. Aim:To analyse the effect of ghrelin administration on food intake regulation in arthritic rats. Methods: Arthritis was induced in adult male Wistar rats by an intradermal injection in the sole of the right paw of 4 mg of complete Freund's adjuvant. On day 6 after adjuvant injection, control and arthritic rats were treated with ghrelin (50 nmol/kg sc) twice a day, until day 15 when all rats were humanly killed. Arthritis induces anorexia, for that reason we included a pair-fed group. Gene expression of leptin receptor and orexigenic peptides: neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the hypothalamus were quantified using RT-PCR. Serum leptin was measured by radioinmunoassay. Results: Arthritis decreased body weight and food intake (P<0,01), but increased AgRP gene expression in the hypothalamus (P<0,01) and decreased serum leptin levels (P<0,01). In control rats, ghrelin administration increased food intake, the two first days of treatment, and body weight (P<0,05). Ghrelin administration increased serum leptin levels in control rats (P<0,05) but not in arthritic rats. In contrast, in arthritic rats ghrelin increased the expression of NPY and AgRP mRNA in the hypothalamus (P<0,01). Conclusion: Although in arthritic rats ghrelin treatment stimulated the expression of orexigenic peptides in the hypothalamus, arthritis seems to induce resistance to the orexigenic action of ghrelin.
Where applicable, experiments conform with Society ethical requirements