Department of Medicine and Physiology & Biophysics
University of Colorado Denver
Regulation of Energy Balance
Grants: 1) NIH R01 DK38088 Utilization of Ingested Energy During Underfeeding
2) NIH DK048520 (Hill) Colorado Clinical Nutrition Research Center
3) NIH R01 DK071692 (Wyatt) Using the Energy Gap to Prevent Weight Regain
4) Komen KG081323 (Anderson/Thor) Modulation of Obesity-Induced Breast Cancer by Metformin
Description of Research
We study the metabolic adaptations to weight loss, how they coordinately work together to promote weight regain, and what therapeutic strategies can be used to counter them. In particular, we employ mature obesity-prone rats to model the process of weight regain in humans and characterize several key aspects of the homeostatic system controlling body weight. We use comprehensive metabolic monitoring systems in combination with in vivo tracers and a number of other approaches to study energy balance, fuel utilization, body composition, adiposity signals, hunger/satiety signals, and tissue-specific changes in skeletal muscle, liver, and adipose tissue that are involved in these adaptations. Finally, we mimic common therapeutic strategies for long term weight reduction (dietary, nutritional, and physical activity) to see how these interventions adjust the biological pressures to regain lost weight.
In collaboration with cancer researchers, we are using the same obesity-prone rodent model to study the increased risk of postmenopausal breast cancer that occurs with obesity, as well as the potential therapeutic interventions that might ameliorate this increased risk. In particular, we chemically-induce mammary carcinogenesis in obesity-prone rats to pursue a better understanding of the key aspects of energy balance, fuel utilization, and changes in peripheral tissue gene expression, which result in increased mammary tumor progression after surgical ovariectomy.
1-2 Most Significant Publications
1) MacLean PS, Higgins JA, Wyatt H, Melanson E, Johnson GC, Jackman MR, Giles ED, Brown I, Hill JO. Regular exercise attenuates the metabolic drive to regain weight after long term weight loss. Am J Physiol Regul Integr Comp Physiol (in press, 2009).
2) MacLean PS, Giles ED, Johnson GC, McDaniel SM, Fleming-Elder BK, Gilman KA, Andrianakos AG, Jackman AR, Shroyer KR, Schedin PJ. A surprising link between the energetics of weight gain and mammary tumor progression in a model of postmenopausal obesity. Obesity (in press, 2009).
Primary Focus Area
· Obesity/Metab Dysregulation
Secondary Focus Areas
· Weight Management
· Adipocyte Biology
· Obesity/Metab Co-Morbidities
· Food Intake Regulation
Access to Specialized Models
· Obesity-prone and obesity-resistant rats
· mCK-CAR transgenic mice, which allows in vivo adenoviral delivery of specific genes in skeletal muscles with site specific injections.
Benefit of CNRU
CNRU provides resources that support basic science research related to in vivo, preclinical measurements of energy balance, fuel utilization, endocrine profiling, gene expression, and adipocytes morphology. The seminar series fosters collegial interaction and collaboration, and the pilot/feasibility projects support the work of jr investigators. This P/F funding gave me my start and allowed me to develop a successful, collaborative research program in my first faculty appointment.
CNRU Cores Used
Administrative, Energy Balance, Metabolic
Jackman, Higgins, Wyatt, Bessesen, Mcmanaman, Melanson, Hill, Eckel, Schedin, Anderson, Thor, Jensen, Kohrt, Jankowski, Van Pelt, Hansen, Neville