Department of Medicine
University of Colorado Denver
Regulation of Energy Balance
1) NIH R01DK38088: (MacLean) Utilization of Ingested Energy During Underfeeding
2) NIH DK048520 (Hill) Colorado Clinical Nutrition Research Center
3) NIH R01DK077992 (VanPelt) Regional Fat Re-accumulation Following Lipectomy in Pre- and Postmenopausal Women
4) NIH R01DK57508 (Kosmiski). Energy Expenditure in HIV Lipodystophy
5) Strategic Initiative Research Committee Grant, (MacLean)
Dean’s Academic Enrichment Fund/NIH. Quantitative magnetic resonance body composition assessment for small animals.
Description of Research
We have observed that the presence or absence of adaptations that occur within the first few days of overfeeding a HFD are critical in determining either the susceptibility or resistance to obesity. Collectively, our data demonstrate that in contrast to OP rats, OR rats rapidly respond to the introduction of a HFD with comprehensive adaptive responses that resist weight gain and promote the maintenance of a thin phenotype. More specifically, there is a coordinated response to overfeeding of a HFD that involves increased energy expenditure, reduced intake, and an increased capacity for fat oxidation. The result is that fat mass is remarkably well maintained in OR rats. Collectively, the findings support the contention that obesity onset and obesity resistance is polygenic in nature. Although our data indicate that multiple systems are involved, preferential trafficking of dietary lipid to oxidative tissues appears to be a key component of the adaptive responses in OR rats.
In following, skeletal muscle is metabolically active and thus is an attractive target for therapeutic interventions and strategies. In following, we are also interested in how differential adaptations in skeletal muscle may differ in obesity prone and obesity resistant rats as they relate to 1) changes in the mitochondrial proteome, including
post-translational modifications, and 2) mitochondrial function
1-2 Most Significant Publications
1) Jackman MR, Steig A, Higgins JA, Johnson GC, Fleming-Elder BK, Bessesen DH, MacLean PS. Weight Regain After Sustained Weight Reduction is Accompanied by Suppressed Oxidation of Dietary Fat and Adipocyte Hyperplasia. Am J Physiol Regul Integr Comp Physiol 294: R1117-R1129, 2008. 33.
2) Jackman MR, MacLean PS, Bessesen DH. Energy expenditure in obesity prone and obesity resistant rats before and after the introduction of a high fat diet. Am J Physiol Regul Integr Comp Physiol (in review 8/09).
Primary Focus Area
· Obesity/Metab Dysregulation
Secondary Focus Areas
· Adipocyte Biology
· Obesity/Metab Co-Morbidities
· Food Intake Regulation
Access to Specialized Models
· Obesity-prone and obesity-resistant rats
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, adipocyte morphology, and proteomic analysis. I have personally benefited from both the seminar series which fosters collegial interaction and collaboration, and the CNRU pilot/feasibility grants which support the work of junior investigators.
CNRU Cores Used
Energy Balance, Metabolic Core
Jackman, Higgins, Bessesen, McManaman, Hill, Eckel, Jensen, Kohrt, Van Pelt, Hansen, Cornier