Studies have suggested that insulin may be a regulator of food intake and body weight by acting at the central nervous system (CNS). This renewal proposal addresses the hypothesis that the ability of insulin to act as a satiety signal may change during normal growth and development, and may be abnorrnal in obesity. Studies are proposed to examine whether insulin uptake into the CNS, or insulin action-in the CNS, is altered in rats as a function of age, gender, and genetic or diet-induced obesity. Insulin uptake by brain will be assessed in vivo by measurement of steady state levels of plasma and CSF insulin during vehicle or insulin infusions. Brain capillary insulin binding sites will be measured as an in vitro estimate of specific receptor-mediated transport capacity. Regulation of these receptors has been observed by this laboratory and others and may represent a potential mechanism for regulation of insulin uptake into the CNS. Insulin action will be assessed behaviorally by measuring body weight and food intake in response to intraventricular insulin infusions. Insulin action in vitro will be assessed by measurement of insulin effects on norepinephrine uptake and post-synaptic events in the hippocampus, a brain region in which I have demonstrated insulin stimulation of phospholipid metabolism which may be mediated locally by catecholamines, as well as in the hypothalamus and olfactory bulb, two brain regions which play a major role in the regulation of food intake and body weight, and compared with changes of peripheral insulin action. Together, these studies should determine whether the effectiveness of the candidate CNS adiposity signal, insulin, is regulated by changes in its uptake and/or action in the CNS.
| Figlewicz, Dianne P; Jay, Jennifer; West, Constance H et al. (2018) Effect of dietary palmitic and stearic acids on sucrose motivation and hypothalamic and striatal cell signals in the rat. Am J Physiol Regul Integr Comp Physiol 314:R191-R200 |
| Figlewicz, Dianne P (2016) Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat: Historical perspective. Brain Res 1645:68-70 |
| Figlewicz, Dianne P (2015) Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective. Psychosom Med 77:664-70 |
| Figlewicz, D P; Hill, S R; Jay, J L et al. (2014) Effect of recurrent yohimbine on immediate and post-hoc behaviors, stress hormones, and energy homeostatic parameters. Physiol Behav 129:186-93 |
| Stice, Eric; Figlewicz, Dianne P; Gosnell, Blake A et al. (2013) The contribution of brain reward circuits to the obesity epidemic. Neurosci Biobehav Rev 37:2047-58 |
| Figlewicz, Dianne P; Jay, Jennifer L; Acheson, Molly A et al. (2013) Moderate high fat diet increases sucrose self-administration in young rats. Appetite 61:19-29 |
| Seaquist, Elizabeth R; Lattemann, Dianne Figlewicz; Dixon, Roger A (2012) American Diabetes Association research symposium: diabetes and the brain. Diabetes 61:3056-62 |
| Overduin, Joost; Figlewicz, Dianne P; Bennett-Jay, Jennifer et al. (2012) Ghrelin increases the motivation to eat, but does not alter food palatability. Am J Physiol Regul Integr Comp Physiol 303:R259-69 |
| Davis, Jon F; Choi, Derrick L; Schurdak, Jennifer D et al. (2011) Leptin regulates energy balance and motivation through action at distinct neural circuits. Biol Psychiatry 69:668-74 |
| Figlewicz, Dianne P; Bennett-Jay, Jennifer L; Kittleson, Sepideh et al. (2011) Sucrose self-administration and CNS activation in the rat. Am J Physiol Regul Integr Comp Physiol 300:R876-84 |
Showing the most recent 10 out of 59 publications
