The initiation and maintenance of ingestive behavior is co-determined by metabolic and non-metabolic factors. Among the latter, environmental cues as well as reward, cognitive and emotional factors play an important role, particularly in human food intake in the modern world. These non-homeostatic factors are processed mainly in cortico-limbic structures such as the prefrontal cortex, amygdala, and ventral striatum. An important issue is to understand how and where metabolic and non-metabolic factors are integrated to drive food intake. The proposed work focuses on one aspect of this issue by examining the anatomical, neurochemical, and functional relationship between the ventral striatum and the hypothalamic peptidergic circuits implicated in the homeostatic regulation of energy balance.
In Aim 1, we identify hypothalamic targets of ventral striatal projections involved in the robust intake of specific foods induced by chemical manipulations within the nucleus accumbens or ventral pallidum, using Fos expression, neuronal tracing, immunohistochemistry, and in situ hybridization.
In Aim 2 we hypothesize that chemical manipulations in the nucleus accumbens stimulate further food intake and override normal homeostatic controls in fully satiated rats by acting on orexigenic and/or anorexigenic hypothalamic signaling systems. We test this by using pharmacological experiments with selective antagonists and agonists against """"""""feeding"""""""" peptide receptors, anatomically localized immunotoxic lesions, and murine knockout models.
In Aim 3 we hypothesize that ventral striatum D hypothalamus projections play an important role in the acute hyperphagic response to palatable foods and in the development of obesity with chronic exposure to palatable diets. To this end, we use two different chronic lesion models that interrupt specific components of ventral striatal-hypothalamic circuitry, and measure both """"""""liking"""""""" and """"""""wanting"""""""" aspects of food intake as well as adiposity and body weight. The results will be important for (1) gaining detailed anatomical and neurochemical insight into the relationship between reward and homeostatic neural systems, (2) the development of a conceptual framework of how the different psychological processes involved in food reward are neurologically organized, and (3) the development of pharmacological and behavioral therapeutic tools to counteract """"""""common"""""""" obesity in a world of plenty.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK071082-04
Application #
7563921
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Hyde, James F
Project Start
2006-02-15
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2011-01-31
Support Year
4
Fiscal Year
2009
Total Cost
$286,759
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Berthoud, Hans-Rudolf; Münzberg, Heike; Morrison, Christopher D (2017) Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms. Gastroenterology 152:1728-1738
Mumphrey, M B; Patterson, L M; Zheng, H et al. (2013) Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1-, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol Motil 25:e70-9
Shin, Andrew C; Berthoud, Hans-Rudolf (2013) Obesity surgery: happy with less or eternally hungry? Trends Endocrinol Metab 24:101-8
Shin, Andrew C; Zheng, Huiyuan; Townsend, R Leigh et al. (2013) Longitudinal assessment of food intake, fecal energy loss, and energy expenditure after Roux-en-Y gastric bypass surgery in high-fat-fed obese rats. Obes Surg 23:531-40
Berthoud, Hans-Rudolf; Zheng, Huiyuan (2012) Modulation of taste responsiveness and food preference by obesity and weight loss. Physiol Behav 107:527-32
Shin, Andrew C; Zheng, Huiyuan; Berthoud, Hans-Rudolf (2012) Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism. Ann Surg 255:294-301
Frutos, Miriam García-San; Pistell, Paul J; Ingram, Donald K et al. (2012) Feed efficiency, food choice, and food reward behaviors in young and old Fischer rats. Neurobiol Aging 33:206.e41-53
Berthoud, Hans-Rudolf (2012) The neurobiology of food intake in an obesogenic environment. Proc Nutr Soc 71:478-87
Berthoud, Hans-Rudolf; Münzberg, Heike; Richards, Brenda K et al. (2012) Neural and metabolic regulation of macronutrient intake and selection. Proc Nutr Soc 71:390-400
Berthoud, Hans-Rudolf (2011) Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr Opin Neurobiol 21:888-96

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