Obesity is one of the most urgent health problems, and all strategies for its prevention or treatment have failed. Increased sedentary behavior represents one reason for the increasing prevalence of obesity and its devastating consequences. Low physical activity levels are also a major determinant of body fat gain during overfeeding. We have recently generated preliminary data indicating that within the established regulatory system controlling food intake and body weight, the novel hormone ghrelin, as well at its main mediating target molecule in the brain AGRP, effectively suppress spontaneous physical activity (SPA) in rodent models. The putative regulation of spontaneous physical activity (SPA) by several other players in the same hormonal and neuronal networks, all of which are known to regulate food intake, has not previously been investigated in a systematic manner. We therefore propose to investigate a possible role for endogenous ghrelin and its immediate hypothalamic targets in the regulation of SPA. This series of studies might add a new and important element to the current model of energy balance regulation. Expanding the current model of food intake control to include a detailed characterization of the hormonal mechanisms regulating physical activity will promote our understanding of one of the major factors causing obesity. Equally important will be to develop a novel functional blueprint of a defined interactive network of pathways in the brain, which simultaneously regulates food intake, thermogenesis and SPA. This strategy may help to develop efficacious pharmacological agents to prevent and treat obesity in the future.
| Heppner, Kristy M; Chaudhary, Nilika; Muller, Timo D et al. (2012) Acylation type determines ghrelin's effects on energy homeostasis in rodents. Endocrinology 153:4687-95 |
| Tong, Jenny; Mannea, Erica; Aime, Pascaline et al. (2011) Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J Neurosci 31:5841-6 |
| Lee, Sang Jun; Kim, Ji Young; Nogueiras, Ruben et al. (2010) PKCzeta-regulated inflammation in the nonhematopoietic compartment is critical for obesity-induced glucose intolerance. Cell Metab 12:65-77 |
| Costanzo-Garvey, Diane L; Pfluger, Paul T; Dougherty, Michele K et al. (2009) KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity. Cell Metab 10:366-78 |
| Kirchner, Henriette; Gutierrez, Jesus A; Solenberg, Patricia J et al. (2009) GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 15:741-5 |
| Reed, Jacquelyn A; Benoit, Stephen C; Pfluger, Paul T et al. (2008) Mice with chronically increased circulating ghrelin develop age-related glucose intolerance. Am J Physiol Endocrinol Metab 294:E752-60 |
| Isken, Frank; Pfeiffer, Andreas F H; Nogueiras, Ruben et al. (2008) Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice. Am J Physiol Endocrinol Metab 295:E350-5 |
| Strassburg, Sabine; Anker, Stefan D; Castaneda, Tamara R et al. (2008) Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats. Am J Physiol Endocrinol Metab 295:E78-84 |
| Nogueiras, Ruben; Veyrat-Durebex, Christelle; Suchanek, Paula M et al. (2008) Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes 57:2977-91 |
| Pfluger, Paul T; Kirchner, Henriette; Gunnel, Susanne et al. (2008) Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol 294:G610-8 |
Showing the most recent 10 out of 16 publications
