Obesity is currently a major health problem that increases the risk of many diseases, including diabetes, heart disease, hypertension and some forms of cancer. The growing prevalence of overweight and obese individuals is attributed, in part, to environmental factors such as the abundance of palatable, energy dense foods that are rich in sugar and fat. High-sugar and high-fat foods also promote overeating and obesity in laboratory animals. The orosensory properties (flavor) of high-sugar and high-fat foods are clearly attractive to animals and contribute to diet-induced overeating. Furthermore, the post-oral actions of these nutrients significantly enhance carbohydrate and fat appetites. Post-oral nutrient actions were initially considered to be exclusively inhibitory (satiating) in nature, but recent findings demonstrate that nutrients have positive (stimulating) postingestive consequences that influence food choice and consumption by conditioning flavor preference and acceptance. The onset of satiation during meals can mask the initial stimulation of intake by post-oral nutrients, which has hindered the study of these early effects. Using a new method, the proposed studies will obtain more specific access to the conditioning process that promotes ingestion in an ongoing meal and confers greater attraction to that food in subsequent meals. Animals that have been consuming a mildly palatable flavored solution paired with post-oral water are shifted to a new flavor paired with post-oral nutrient, and the changes in their ingestive responses are monitored. Increased intake in the first session of intestinal nutrient stimulation indicates that the nutrient has been detected and a signal has reached the brain. With additional methods, including the use of knockout mouse models missing elements of putative sensing and signaling mechanisms, the components of this associative process will be investigated. The overall goal of this application is to determine the processes by which orosensory and post-oral sensory stimuli become linked in the acquisition of carbohydrate and fat appetite.
The specific aims of this project are to 1) Investigate carbohydrate stimulation of intake and flavor preference learning;2) Investigate fat stimulation of intake and flavor preference learning;and 3) Evaluate the role of fat taste and post-oral feedback on fat appetite and individual differences in nutrient preferences. This research involves the fields of psychology, nutrition, and gastrointestinal physiology. Understanding how flavors become linked to rewarding properties of foods, strengthening preferences and leading to overeating is crucial to finding ways to limit the intake-promoting effects of foods. This knowledge may also be applied to promote eating in clinical cases of anorexia and cachexia.

Public Health Relevance

This project will examine the processes by which carbohydrates and fats stimulate eating and lead to preferences for foods high in these nutrients. Discovering the controls of nutrient-stimulated eating will assist the development of treatments for overeating and obesity as well as for anorexia.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Yanovski, Susan Z
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Brooklyn College
Schools of Arts and Sciences
New York
United States
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Sclafani, Anthony; Vural, Austin S; Ackroff, Karen (2018) Profound differences in fat versus carbohydrate preferences in CAST/EiJ and C57BL/6J mice: Role of fat taste. Physiol Behav 194:348-355
Sclafani, Anthony (2018) From appetite setpoint to appetition: 50years of ingestive behavior research. Physiol Behav 192:210-217
Spector, Alan C; le Roux, Carel W; Munger, Steven D et al. (2017) Proceedings of the 2015 ASPEN Research Workshop-Taste Signaling. JPEN J Parenter Enteral Nutr 41:113-124
Sclafani, Anthony; Ackroff, Karen (2017) Flavor preferences conditioned by nutritive and non-nutritive sweeteners in mice. Physiol Behav 173:188-199
Sclafani, Anthony; Vural, Austin S; Ackroff, Karen (2017) CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose. Chem Senses 42:259-267
Glendinning, John I; Frim, Yonina G; Hochman, Ayelet et al. (2017) Glucose elicits cephalic-phase insulin release in mice by activating KATP channels in taste cells. Am J Physiol Regul Integr Comp Physiol 312:R597-R610
Ackroff, Karen; Sclafani, Anthony (2016) Flavor Preferences Conditioned by Dietary Glutamate. Adv Nutr 7:845S-52S
Sclafani, Anthony; Adamantidis, Antoine; Ackroff, Karen (2016) MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice. Physiol Behav 163:239-244
Sclafani, Anthony (2016) Bypassing Intestinal Sugar Enhancement of Sweet Appetite. Cell Metab 23:3-4
Kraft, Tamar T; Huang, Donald; Lolier, Melanie et al. (2016) BALB/c and SWR inbred mice differ in post-oral fructose appetition as revealed by sugar versus non-nutritive sweetener tests. Physiol Behav 153:64-9

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