Linking hepatic transcriptional changes to high-fat diet induced physiology for diabetes-prone and obese-resistant mice.
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 twelve weeks to transcriptionally profile the liver for changes caused by high fat diet. In the eighth 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.
Alevizos
Ilias
I
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Misra
Jatin
J
Bullen
John
J
Basso
Giuseppe
G
Kelleher
Joanne
J
Mantzoros
Christos
C
Stephanopoulos
Gregory
G
D050153:Abdominal Fat / Q000033:anatomy & histology; D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology*; D020869:Gene Expression Profiling; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic
D004041:Dietary Fats; D007328:Insulin; D020738:Leptin