Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice

Enpeng Zhao, Mark P. Keller, Mary E. Rabaglia, Angie T. Oler, Donnie S. Stapleton, Kathryn L. Schueler, Elias Chaibub Neto, Jee Young Moon, Ping Wang, I. Ming Wang, Pek Yee Lum, Irena Ivanovska, Michele Cleary, Danielle Greenawalt, John Tsang, Youn Jeong Choi, Robert Kleinhanz, Jin Shang, Yun Ping Zhou, Andrew D. HowardBei B. Zhang, Christina Kendziorski, Nancy A. Thornberry, Brian S. Yandell, Eric E. Schadt, Alan D. Attie

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Type 2 diabetes results from severe insulin resistance coupled with a failure of β cells to compensate by secreting sufficient insulin. Multiple genetic loci are involved in the development of diabetes, although the effect of each gene on diabetes susceptibility is thought to be small. MicroRNAs (miRNAs) are noncoding 19-22-nucleotide RNA molecules that potentially regulate the expression of thousands of genes. To understand the relationship between miRNA regulation and obesity-induced diabetes, we quantitatively profiled approximately 220 miRNAs in pancreatic islets, adipose tissue, and liver from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mice. More than half of the miRNAs profiled were expressed in all three tissues, with many miRNAs in each tissue showing significant changes in response to genetic obesity. Furthermore, several miRNAs in each tissue were differentially responsive to obesity in B6 versus BTBR mice, suggesting that they may be involved in the pathogenesis of diabetes. In liver there were approximately 40 miRNAs that were downregulated in response to obesity in B6 but not BTBR mice, indicating that genetic differences between the mouse strains play a critical role in miRNA regulation. In order to elucidate the genetic architecture of hepatic miRNA expression, we measured the expression of miRNAs in genetically obese F2 mice. Approximately 10% of the miRNAs measured showed significant linkage (miR-eQTLs), identifying loci that control miRNA abundance. Understanding the influence that obesity and genetics exert on the regulation of miRNA expression will reveal the role miRNAs play in the context of obesity-induced type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)476-485
Number of pages10
JournalMammalian Genome
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Genetics

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    Zhao, E., Keller, M. P., Rabaglia, M. E., Oler, A. T., Stapleton, D. S., Schueler, K. L., Neto, E. C., Moon, J. Y., Wang, P., Wang, I. M., Lum, P. Y., Ivanovska, I., Cleary, M., Greenawalt, D., Tsang, J., Choi, Y. J., Kleinhanz, R., Shang, J., Zhou, Y. P., ... Attie, A. D. (2009). Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice. Mammalian Genome, 20(8), 476-485. https://doi.org/10.1007/s00335-009-9217-2