Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic Capacity in Diabetes Susceptibility
- Hong Lan1,
- Mary E. Rabaglia1,
- Jonathan P. Stoehr1,
- Samuel T. Nadler1,
- Kathryn L. Schueler1,
- Fei Zou2,
- Brian S. Yandell3 and
- Alan D. Attie1
- 1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin
- 2Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina
- 3Department of Statistics and Horticulture, University of Wisconsin, Madison, Wisconsin
Abstract
Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistant. We used DNA microarrays and RT-PCR to compare the gene expression in BTBR-ob/ob versus B6-ob/ob mice in adipose tissue, liver, skeletal muscle, and pancreatic islets. Our results show: 1) there is an increased expression of genes involved in inflammation in adipose tissue of diabetic mice; 2) lipogenic gene expression was lower in adipose tissue of diabetes-susceptible mice, and it continued to decrease with the development of diabetes, compared with diabetes-resistant obese mice; 3) hepatic expression of lipogenic enzymes was increased and the hepatic triglyceride content was greatly elevated in diabetes-resistant obese mice; 4) hepatic expression of gluconeogenic genes was suppressed at the prediabetic stage but not at the onset of diabetes; and 5) genes normally not expressed in skeletal muscle and pancreatic islets were expressed in these tissues in the diabetic mice. We propose that increased hepatic lipogenic capacity protects the B6-ob/ob mice from the development of type 2 diabetes.
Footnotes
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Address correspondence and reprint requests to Alan D. Attie, Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Dr., Madison, WI, 53706. E-mail: attie{at}biochem.wisc.edu.
Received for publication 16 October 2002 and accepted in revised form 18 November 2002.
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
ACO, Acyl CoA oxidase; CT, threshold cycle; dChip, DNA-Chip analyzer; IL, interleukin; PEPCK, phosphoenopyruvate carboxykinase; PPAR-α, peroxisome proliferator–activator receptor-α; SREBP, sterol regulatory element binding protein; TG, triglyceride.
- DIABETES
