Item Details

Uncoupling Obesity From Insulin Resistance - a Genetic Screen for Fat Content Suppressors Using C. Elegans Model of Insulin Resistance

Michaels, Kerry
Format
Thesis/Dissertation; Online
Author
Michaels, Kerry
Advisor
Deppmann, Christopher
Abstract
Abstract Insulin resistance and obesity are the two major risk factors for metabolic syndrome. It has long been thought that shutting down the insulin signaling pathway should promote fat burning similar to starvation scenarios. It is observed however that patients with insulin resistance do not always seem to lose weight. Instead, excess fat accumulation persists despite their insulin resistant state. This creates a vicious cycle, where persistent obesity continues to promote insulin resistance often resulting in type two diabetes. Genetic mouse models lacking the insulin receptor in adipose tissue do not follow this disease model. Instead, they more predictably fail to accumulate fat stores. The model organism, C. elegans, presents many advantages in determining how fat dysregulation and adult-onset insulin resistance are linked. Strains carrying a temperature sensitive mutation of the daf-2 insulin receptor become obese when shifted to the non-permissive temperature as adults. A reverse-genetic screen was conducted to find gene inactivations, which suppress the obese phenotype in this model. We identified a number of novel metabolic regulators. We further identified one, hlh-16, which shares homology with an eye-development gene in humans. We propose this transcription factor may also regulate lipid metabolism, and present evidence that it effects transcriptional levels of fatty-acid elongase, elo-2.
Language
English
Date Received
20151202
Published
University of Virginia, Department of Biology, MS (Master of Science), 2015
Published Date
2015-12-01
Degree
MS (Master of Science)
Collection
Libra ETD Repository
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