Hormonal and metabolic factors signal the status of energy balance to hypothalamic nuclei.
Obesity is characterized by neuronal, metabolic and hormonal alterations. We therefore hypothesized that hypothalamic responses to challenges of energy balance may differ between lean and obese animals. To test this, we compared c-Fos expression in the hypothalamic arcuate (
ARC) and paraventricular nuclei (PVN) and the lateral hypothalamic area (LHA) of mice (1-year-old) with late-onset
obesity (LOO) and of lean controls under different feeding conditions. Fourteen hours of fasting induced high c-Fos expression in
neuropeptide-Y-positive
ARC neurons, in the PVN and in the rostral LHA in lean but not in LOO mice. c-Fos expression in
melanin-concentrating hormone (MCH) and
orexin-containing neurons in the caudal LHA was not affected by fasting. LOO mice showed fasting
hyperinsulinemia, hyperleptinemia, elevated fasting
blood glucose and an attenuated hyperphagic response during refeeding. Moreover, the
anorectic response to
leptin and
hypoglycemic response to
insulin were reduced in LOO mice. We conclude that adiposity blunts the neuronal responses to metabolic challenges in hypothalamic centers which control feeding behavior and energy balance. Elevated
blood glucose may be one factor that suppresses hypothalamic responsiveness in obese mice. A similar impact of
hyperinsulinemia and hyperleptinemia in LOO mice is also likely although under the current experimental conditions responsiveness to some effects of these
hormones appeared to be reduced.