The research proposed in this grant attempts to display the integrative physiology in the upper gastrointestinal tract and to relate features of this physiology to the control of food intake. The program, therefore, has both a physiological and a behavioral aspect and important health related findings can be expected from both. Rhesus monkeys and rats will be the experimental subjects. The following experiments are devised. 1) A definition of the integrative mechanisms relating the stomach's emptying to the contents of the intestine by displaying changes in the delivery of liquids from the stomach when nutrients are placed in the intestine and when intravenous infusions of gut hormones are given. This will demonstrate that the nutrients and the hormones that they release from the intestine such as cholecystokinin (CCK) will coordinate the stomach's emptying and by reducing the amount of a meal passing into the intestine cause the stomach to retain food and to distend. 2) A demonstration that contents of the stomach and the intestine can inhibit food intake. Infusions of nutrients into the intestine and intravenous infusions of gut hormones such as CCK will be studied alone or with distending loads of non-nutrient physiological saline in the stomach for effects on the consumption of sucrose solutions and monkey chow. A gastric balloon will test the inhibition on food intake from stomach distention alone. These experiments challenge the hypothesis that a major inhibition on food intake comes from the distended stomach. 3) A display of the receptor sites for gut hormones to determine their likely role in physiology and behavior. In vitro receptor autoradiography will be employed to demonstrate CCK, bombesin and other gut hormone receptor sites. 4) Demonstration of the physiological and behavioral effects of surgical disconnections of the gastric outlet by pyloroplasty and off the neural links from stomach to brain by vagotomy. This will also test the hypothesis that distention of the stomach provoked by intestinal nutrients and gut hormones during feeding produced a termination of feeding by sensations carried through the vagus nerve. Knowledge of this basic physiology and functional relationships to feeding behavior is crucial to any effort to define the pathophysiology and therefore the most appropriate treatments for such digestive disorders as peptic ulcer and alimentary hypoglycemia and behavioral disorders such as obesity, anorexia nervosa and bulimia.
| Beheshti, Rahmatollah; Treesukosol, Yada; Igusa, Takeru et al. (2018) A predictive model of rat calorie intake as a function of diet energy density. Am J Physiol Regul Integr Comp Physiol 315:R256-R266 |
| Treesukosol, Yada; Inui-Yamamoto, Chizuko; Mizuta, Haruno et al. (2018) Short-Term Exposure to a Calorically Dense Diet Alters Taste-Evoked Responses in the Chorda Tympani Nerve, But Not Unconditioned Lick Responses to Sucrose. Chem Senses 43:433-441 |
| Treesukosol, Yada; Moran, Timothy H (2018) Cross-Generalization Profile to Orosensory Stimuli of Rats Conditioned to Avoid a High Fat/High Sugar Diet. Chem Senses 43:181-188 |
| Smedh, Ulrika; Scott, Karen A; Moran, Timothy H (2018) Fourth ventricular thyrotropin induces satiety and increases body temperature in rats. Am J Physiol Regul Integr Comp Physiol 314:R734-R740 |
| Chawla, Anjali; Cordner, Zachary A; Boersma, Gretha et al. (2017) Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder. Physiol Behav 180:78-90 |
| Yang, Yan; Choi, Pique P; Smith, Wanli W et al. (2017) Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus. Sci Rep 7:6936 |
| Moghadam, Alexander A; Moran, Timothy H; Dailey, Megan J (2017) Alterations in circadian and meal-induced gut peptide levels in lean and obese rats. Exp Biol Med (Maywood) 242:1786-1794 |
| Dailey, Megan J; Moran, Timothy H; Holland, Peter C et al. (2016) The antagonism of ghrelin alters the appetitive response to learned cues associated with food. Behav Brain Res 303:191-200 |
| Boersma, Gretha J; Tamashiro, Kellie L; Moran, Timothy H et al. (2016) Corticosterone administration in drinking water decreases high-fat diet intake but not preference in male rats. Am J Physiol Regul Integr Comp Physiol 310:R733-43 |
| Moran, Timothy H; Ladenheim, Ellen E (2016) Physiologic and Neural Controls of Eating. Gastroenterol Clin North Am 45:581-599 |
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