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OMENTECTOMY IN THE CANINE: A UNIQUE MODEL TO INVESTIGATE THE PHYSIOLOGIC RELATIONSHIP BETWEEN VISCERAL FAT AND INSULIN ACTION by Maya Lottati __________________________________________________________ A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHYSIOLOGY AND BIOPHYSICS) August 2008 Copyright 2008 Maya Lottati
|Title||Omentectomy in the canine: a unique model to investigate the physiologic relationship between visceral fat and insulin action|
|Degree||Doctor of Philosophy|
|Degree program||Physiology & Biophysics|
|School||Keck School of Medicine|
|Advisor (committee chair)||Bergman, Richard N.|
|Advisor (committee member)||
Meiselman, Herbert J.
Buchanan, Thomas A.
Watanabe, Richard M.
|Abstract||Visceral obesity is associated with a variety of chronic diseases including type 2 diabetes and cardiovascular disease. A reduction in visceral fat by omentectomy improves the metabolic profile in humans, suggesting that visceral fat impairs insulin sensitivity (SI). We tested this hypothesis by examining the effects of omentectomy on metabolic function in non-obese dogs. Omentectomy failed to generate measurable changes in body weight (P=0.10), or subcutaneous adiposity (P=0.83). The removal of the greater omentum, which resulted in a diminutive 7% reduction in visceral fat (P=0.29), markedly enhanced SI 64% (P=0.03) particularly in peripheral tissues. These data provide compelling evidence for the deleterious role of visceral fat in insulin resistance, however the mechanism remains unclear.; Free fatty acids (FFA) have been suggested to mediate visceral obesity and insulin resistance. We examined 24-hour plasma profiles of FFA and adipokines to identify putative signal(s) that may modulate SI following omentectomy in obese dogs. Visceral fat was reduced 16% (P=0.005) and was accompanied by an 18% improvement in SI (P=0.01). Although we observed no variations in 24-hour adiponectin (P=0.58) or the inflammatory marker C-reactive protein (P=0.19), FFA were diminished at all times during the day resulting in a 22% reduction in area under the curve (P=0.03). Moreover, changes in FFA were correlated with SI improvements (P=0.03), suggesting that a reduction in FFA, not adipokines, modulate SI with reduced visceral fat. Thus, visceral fat-derived FFA may induce insulin resistance with truncal-obesity.; The effects of omentectomy have conflicting results in humans. To examine the efficacy of omentectomy as a long-term therapeutic option, omentectomized- and sham-treated dogs were challenged with a high-fat diet to determine relative susceptibility to obesity and insulin resistance. While there was no difference in the progression to insulin resistance between groups (P=0.72), omentectomized-dogs were unable to compensate with hyperinsulinemia (P=0.39), suggesting pancreatic beta-cell impairment. Hence, while omentectomy produces impressive short-term improvements in SI, results in the dog model suggest omentectomy will not provide enduring benefits for metabolic co-abnormalities of central-obesity in humans. Further studies are necessary to determine molecular role of the greater omentum in determination of SI, diurnal FFA, and β-cell compensation.|
|Keyword||visceral fat; insulin resistance; omentectomy|
|Part of collection||University of Southern California dissertations and theses|
|Publisher (of the original version)||University of Southern California|
|Place of publication (of the original version)||Los Angeles, California|
|Publisher (of the digital version)||University of Southern California. Libraries|
|Legacy record ID||usctheses-m1286|
|Repository name||Libraries, University of Southern California|
|Repository address||Los Angeles, California|
|Full text||OMENTECTOMY IN THE CANINE: A UNIQUE MODEL TO INVESTIGATE THE PHYSIOLOGIC RELATIONSHIP BETWEEN VISCERAL FAT AND INSULIN ACTION by Maya Lottati __________________________________________________________ A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHYSIOLOGY AND BIOPHYSICS) August 2008 Copyright 2008 Maya Lottati|