Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic Capacity in Diabetes Susceptibility

• Published in: Diabetes (New York, N.Y.) Vol. 52; no. 3; pp. 688 - 700
• Main Authors: Lan, Hong, Rabaglia, Mary E., Stoehr, Jonathan P., Nadler, Samuel T., Schueler, Kathryn L., Zou, Fei, Yandell, Brian S., Attie, Alan D.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2003
• Subjects: Adipocytes; Adipose Tissue - metabolism; Algorithms; Animals; Biological and medical sciences; Body fat; Development and progression; Diabetes; Diabetes Mellitus - genetics; Diabetes Mellitus, Type 2 - genetics; Disease susceptibility; Fatty acids; Fatty Liver - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genetic aspects; Genetic Predisposition to Disease; Gluconeogenesis - genetics; Glucose; Health aspects; Hyperglycemia; Insulin resistance; Islets of Langerhans - metabolism; Lipids - biosynthesis; Liver - enzymology; Liver - metabolism; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal - metabolism; Musculoskeletal system; Mutation; Obesity; Obesity - genetics; Oligonucleotide Array Sequence Analysis; Overweight persons; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sterols; Triglycerides - blood; Triglycerides - metabolism; Type 2 diabetes; United States
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/diabetes.52.3.688

Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic Capacity in Diabetes Susceptibility Hong Lan 1 , Mary E. Rabaglia 1 , Jonathan P. Stoehr 1 , Samuel T. Nadler 1 , Kathryn L. Schueler 1 , Fei Zou 2 , Brian S. Yandell 3 and Alan D. Attie 1 1 Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 2 Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 3 Department 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 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; C T , 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