Obesity has become a major public health problem worldwide such .that in developed countries 10-20% of the adult population is obese. As the rates of obesity rise, so do associated health care costs. Few effective approaches for reducing body weight exist. Current therapeutic tools such as dietary intervention, exercise regimens, behavioral modification and even pharmacological approaches remain disappointing. The development of alternative, effective dietary regimens has significant clinical implications. Identification of efficacious dietary approaches to weight loss could provide a means by which obesity rates are curbed with significantly fewer health risks than those associated with pharmacologic or surgical interventions. Our recent work has demonstrated that hypothalamic signaling, responses to food deprivation, and sensitivity to peptides that either stimulate or inhibit food intake are dependent upon the background diet of the animal. Our overall hypothesis is that dietary macronutrients differentially influence regulatory responses to food intake. Characterization of how dietary macronutrients influence feeding-regulatory systems in terms of acute and chronic adaptive responses to maintenance on these types of diets may identify novel dietary approaches to weight management. There are three specific aims to this project.
The first aim will evaluate the effects of dietary macronutrients on hypothalamic gene expression.
The second aim will identify neural and endocrine systems that are affected by low carbohydrate diets.
The final aim will assess how chronic exposure to ketone bodies affects feeding, body weight, and endocrine and hypothalamic controls of food intake. These experiments are necessary to further our understanding of how macronutrients influence food intake and body weight, and the mechanisms underlying differential feeding responses to chronic consumption of macronutrient-controlled diets. Furthering the basic understanding of relative contributions of dietary macronutrients to overall food intake and body weight has significant clinical implications in an environment where obesity-related disability and death continue to rise.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Yanovski, Susan Z
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Purdue University
Schools of Arts and Sciences
West Lafayette
United States
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Hargrave, Sara L; Davidson, Terry L; Zheng, Wei et al. (2016) Western diets induce blood-brain barrier leakage and alter spatial strategies in rats. Behav Neurosci 130:123-35
Hargrave, Sara L; Davidson, Terry L; Lee, Tien-Jui et al. (2015) Brain and behavioral perturbations in rats following Western diet access. Appetite 93:35-43
Honors, Mary Ann; Kinzig, Kimberly P (2014) Chronic exendin-4 treatment prevents the development of cancer cachexia symptoms in male rats bearing the Yoshida sarcoma. Horm Cancer 5:33-41
Honors, Mary Ann; Kinzig, Kimberly P (2014) Diet-induced obesity and insulin resistance spur tumor growth and cancer cachexia in rats bearing the Yoshida sarcoma. Nutr Cancer 66:872-8
Honors, Mary Ann; Kinzig, Kimberly P (2013) Characterization of the Yoshida sarcoma: a model of cancer cachexia. Support Care Cancer 21:2687-94
Hargrave, Sara L; Kinzig, Kimberly P (2012) Repeated gastric distension alters food intake and neuroendocrine profiles in rats. Physiol Behav 105:975-81
Honors, Mary A; Hargrave, Sara L; Kinzig, Kimberly P (2012) Glucose tolerance in response to a high-fat diet is improved by a high-protein diet. Obesity (Silver Spring) 20:1859-65
Kinzig, Kimberly P; Hargrave, Sara L (2010) Adolescent activity-based anorexia increases anxiety-like behavior in adulthood. Physiol Behav 101:269-76
Kinzig, Kimberly P; Honors, Mary Ann; Hargrave, Sara L (2010) Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology 151:3105-14
Kinzig, Kimberly P; Honors, Mary Ann; Hargrave, Sara L et al. (2010) Sensitivity to the anorectic effects of leptin is retained in rats maintained on a ketogenic diet despite increased adiposity. Neuroendocrinology 92:100-11

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