Food availability and quality in desert habitats is spatially and temporally unpredictable, and animals face periods of food shortage. The golden spiny mouse (Acomys russatus) is an omnivorous desert rodent that does not hoard food, necessitating its withstanding such periods by physiological means alone. In response to food restriction, plasma leptin concentrations, core body temperature and energy expenditure of the spiny mouse decrease significantly after 24 hours, and most spiny mouse are able to maintain their body mass on ca 85% of ad libitum for a prolonged period of time. Both one day food deprivation and long-term food restriction had a significant effect on body mass and plasma leptin concentrations (which decreased significantly with a high correlation) as well as on the orexigenic Agrp (which increased significantly as a result of the 24 h food deprivation); and on NPY (in which the increase was more pronounced under long-term food restriction); but had no effect on the anorexigenic POMC and CART. Leptin administration to food-restricted spiny mice did not affect food intake or the rate of decrease in body mass, indicating that it can not overcome the drive to eat when food is scarce. However it did result in a significant decrease in NPY levels, and the spiny mice spent less time at low body temperatures compared to PBS-treated golden spiny mice. These results show that in food- restricted golden spiny mice leptin affects thermogenesis but not food consumption, and suggest that the thermoregulatory effects of leptin are mediated by NPY.