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Linking Hepatic Transcriptional Changes to High–Fat Diet Induced Physiology for Diabetes-Prone and Obese-Resistant Mice

Ilias Alevizos, Jatin Misra, John Bullen, Giuseppe Basso, Joanne Kelleher, Christos Mantzoros and Gregory Stephanopoulos

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Insulin resistance is characterized by high insulin levels and decreased responsiveness of tissues to the clearance of glucose from the bloodstream. This study maintained the diabetes-prone C57BL/6J and obese-resistant A/J mice strains on a high-fat diet for 12 weeks to transcriptionally profile the liver for changes caused by high fat diet. In the 8th week of the experiment, the C57BL/6J mice began exhibiting signs of insulin resistance, while the A/J mice did not show any such indications during the course of the experiment. A regression model of partial least squares between serum insulin measurements and the liver gene expression profile for the C57BL/6J mice on a high-fat diet was constructed in an effort to quantitatively link the physiological measurement with the gene expressions. A series of discriminating genes between high fat and chow fed mice was generated for both the C57BL/6J and A/J strains. These discriminatory genes contain information about the mechanisms responsible for the development of insulin resistance, and the compensation for a high fat diet, respectively. The results identified several genes involved in the development of insulin resistance and serve as a framework for other studies involving other organs affected by this systemic disease.

Authors

Ilias Alevizos

Massachusetts Institute of Technology, Cambridge, Massachusetts

Jatin Misra

Massachusetts Institute of Technology, Cambridge, Massachusetts

John Bullen

Harvard Medical School, Boston, Massachusetts

Giuseppe Basso

University of Padova, Padova, Italy

Joanne Kelleher

Massachusetts Institute of Technology, Cambridge, Massachusetts

Christos Mantzoros

Harvard Medical School, Boston, Masscahusetts

Gregory Stephanopoulos

Massachusetts Institute of Technology, Cambridge, Massachusetts

Purchase article for $19

Subscribe to this journal for $129/year