Weight regain after weight loss continues to be one of the biggest obstacles to treating obesity. Weight reduction leads to strong metabolic adaptations that promote rapid and efficient regain. The objectives of this work are to identify comprehensive therapeutic strategies that will counter these metabolic pressures in order to facilitate long-term weight reduction. Studying these pressures in humans is challenging because of the difficulty in controlling genetic, environmental, and behavioral influences on energy homeostasis. We have developed an experimental paradigm that closely models human regain, provides better control of these other factors, and has well-defined outcomes that specifically describe the metabolic pressures. This paradigm will be employed to characterize the efficacy of two nutritional approaches to weight management and to study a controversial issue related to fuel utilization during the relapse process. In the first specific aim, we propose to examine a low carbohydrate, high protein (LC-HP) diet and a diet high in resistant starch (RS) fiber for their ability to attenuate the metabolic propensity to regain weight after prolonged weight reduction. Because regular exercise is more commonly prescribed than implemented, these strategies will be tested to see if they are effective without exercise, require exercise to be beneficial, or have no effect regardless of the level of physical activity. In the second aim of this proposal, we propose to examine the utilization of ingested fats during the early stages of relapse to assess whether excess calories and compensatory adjustments in peripheral tissues divert ingested lipids away from oxidation and toward storage in adipose tissue. This alternative to the controversial """"""""glucose redistribution hypothesis"""""""" may provide a better description the changes in fuel utilization that facilitate rapid and efficient weight regain early in the process of relapse.
The first aim will provide practical information about how two nutritional strategies, with or without exercise, affect the metabolic drive to regain weight, and the second aim will provide mechanistic insight into a controversial aspect of the weight regain process. Relevance to Public Health Overcoming the metabolic propensity to regain weight may be the most critical consideration in our fight to control the obesity epidemic. This work will provide valuable information regarding the process of weight regain and the ability of nutritional strategies to alter the metabolic drive to regain weight. These studies may provide important evidence on which to base strategies that will facilitate sustained weight reduction in obese individuals.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
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Yanovski, Susan Z
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University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
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Rudolph, M C; Young, B E; Lemas, D J et al. (2017) Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI. Int J Obes (Lond) 41:510-517
Giles, Erin D; Jackman, Matthew R; MacLean, Paul S (2016) Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females. Front Nutr 3:50
Giles, Erin D; Hagman, Jennifer; Pan, Zhaoxing et al. (2016) Weight restoration on a high carbohydrate refeeding diet promotes rapid weight regain and hepatic lipid accumulation in female anorexic rats. Nutr Metab (Lond) 13:18
Giles, Erin D; Steig, Amy J; Jackman, Matthew R et al. (2016) Exercise Decreases Lipogenic Gene Expression in Adipose Tissue and Alters Adipocyte Cellularity during Weight Regain After Weight Loss. Front Physiol 7:32
MacLean, P S; Higgins, J A; Giles, E D et al. (2015) The role for adipose tissue in weight regain after weight loss. Obes Rev 16 Suppl 1:45-54
Hernandez, Teri L; Bessesen, Daniel H; Cox-York, Kimberly A et al. (2015) Femoral lipectomy increases postprandial lipemia in women. Am J Physiol Endocrinol Metab 309:E63-71
Bessesen, Daniel H; Cox-York, Kimberly A; Hernandez, Teri Lynn et al. (2015) Postprandial triglycerides and adipose tissue storage of dietary fatty acids: impact of menopause and estradiol. Obesity (Silver Spring) 23:145-53
Morris, E Matthew; Jackman, Matthew R; Johnson, Ginger C et al. (2014) Intrinsic aerobic capacity impacts susceptibility to acute high-fat diet-induced hepatic steatosis. Am J Physiol Endocrinol Metab 307:E355-64
Higgins, Janine A (2014) Resistant starch and energy balance: impact on weight loss and maintenance. Crit Rev Food Sci Nutr 54:1158-66
Saben, Jessica L; Bales, Elise S; Jackman, Matthew R et al. (2014) Maternal obesity reduces milk lipid production in lactating mice by inhibiting acetyl-CoA carboxylase and impairing fatty acid synthesis. PLoS One 9:e98066

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