Diet composition plays a significant role in the development of human obesity. A genetic propensity towards dietary obesity has been identified in rodents, and obese individuals demonstrate differences in food preferences from lean individuals. In rodent models, dietary-induced obesity is associated with decreased sensitivity to exogenous administration of the candidate adiposity signal insulin. This suggests that some difference-metabolic, neurochemical, or both-as a consequence of eating a highly palatable, high energy diet is present, resulting in a change in the physiological regulation of body adiposity. Activation of the CNS mesolimbic dopamine (DA) neurons is implicated in the reinforcing or rewarding aspects of several classes of stimuli, including food. We have obtained preliminary evidence that insulin can downregulate the activity of these DA neurons, both at the level of the synapse and at the level of behavior. In this proposal, we pursue the hypothesis that activity of these neurons is altered in association with dietary obesity, and that there is a loss of insulin-induced downregulation of DA neuronal activity. To test this hypothesis, we will evaluate performance in two behavioral tasks in which DA has been implicated: lick rates of sweet and fat solutions, and the conditioned place preference (CPP) paradigm; release of DA from the mesolimbic DA neurons by in vivo microdialysis; and the cellular mechanisms underlying altered DA release, using our established methodologies. All studies will utilize normal weight and dietary obese rats (both outbred rats, and the inbred dietary-induced obese (DIO)/dietary obese-resistant (DR) rats, which are genotypically distinct in their propensity to develop dietary obesity), infused with intraventricular (IVT) vehicle or insulin. Together, these studies will evaluate the ability of a candidate adiposity signal to interact with brain pathways associated with reward; and the influence of palatable high energy diets on the function and regulation of the mesolimbic DA neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040963-16
Application #
6634948
Study Section
Nutrition Study Section (NTN)
Program Officer
Yanovski, Susan Z
Project Start
1988-09-01
Project End
2004-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
16
Fiscal Year
2003
Total Cost
$264,841
Indirect Cost
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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

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