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THE AGING RODENT: INSULIN RESISTANCE, OBESITY, AND
METABOLIC COMPENSATION
by
Karyn Joanne Catalano
____________________________________________________
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)
December 2007
Copyright 2007 Karyn Joanne Catalano
Object Description
| Title | The aging rodent: insulin resistance, obesity, and metabolic compensation |
| Author | Catalano, Karyn Joanne |
| Author email | kcatalan@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Physiology & Biophysics |
| School | Keck School of Medicine |
| Date defended/completed | 2007-08-01 |
| Date submitted | 2007 |
| Restricted until | Unrestricted |
| Date published | 2007-09-06 |
| Advisor (committee chair) | Bergman, Richard N. |
| Advisor (committee member) |
Watts, Alan G. Youn, Jang Chow, Robert |
| Abstract | Aging is characterized by obesity, insulin resistance, glucose intolerance and an increased prevalence of the metabolic syndrome. It has been suggested that age-associated insulin resistance is due to concomitant increases in adiposity, rather than aging per se. In particular, intra-abdominal obesity has been implicated, suggesting that intra-abdominal fat mass, regardless of the manner in which it is accumulated, is responsible for insulin resistance. To test this hypothesis, I measured insulin sensitivity (SI) and intra-abdominal adiposity in young fat-fed and old rats of varying degrees of obesity. Insulin-stimulated glucose uptake was similarly impaired (p=0.58) in young and old obese rats, despite greater intra-abdominal adiposity in young obese rats. Interestingly, regression analyses separated for age revealed that older rats exhibit a proportionately greater decrement in SI with equivalent increase in adiposity, suggesting that in rodents, youth affords significant protection against obesity-induced insulin resistance.; To determine if this phenomenon persists during weight loss as well as the potential involvement of true visceral fat (the mesenteric fat depot) in this altered susceptibility, I subjected young fat-fed and old rats of similar degrees of resistance to short-term caloric restriction (CR). Despite similar losses in body weight and visceral fat (p=0.54), old animals experienced significantly less improvement in insulin sensitivity (33%) with CR than did young fat fed rats (83%). These data provide additional support for the hypothesis that old rats have an increased susceptibility to visceral fat-induced insulin resistance.; Finally, while it is well-documented that older animals are insulin resistant, it is unclear whether adequate metabolic compensation is employed to counter resistance. To examine this, I measured metabolic compensation in older rats. Insulin resistance was partially compensated for by >2-fold larger insulin response in OL compared to Y (p=0.013). However, glucose effectiveness, or the ability of glucose to modulate its own metabolism, was not altered (p=0.79). Thus, aged rodents appear to exhibit partial hyperinsulinemic compensation with not apparent contribution from increased glucose effectiveness. Further studies will be necessary todetermine the mechanisms responsible for compensatory hyperinsulinemia in the aged rodent, as well as the increased susceptibility in older animals to obesity-related insulin resistance. |
| Keyword | aging; insulin resistance; visceral obesity |
| Language | English |
| 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 |
| Type | texts |
| Legacy record ID | usctheses-m807 |
| Rights | Catalano, Karyn Joanne |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Catalano-20070906 |
| Archival file | uscthesesreloadpub_Volume23/etd-Catalano-20070906.pdf |
Description
| Title | Page 1 |
| Full text | THE AGING RODENT: INSULIN RESISTANCE, OBESITY, AND METABOLIC COMPENSATION by Karyn Joanne Catalano ____________________________________________________ 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) December 2007 Copyright 2007 Karyn Joanne Catalano |
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