title: Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice.
abstract: Type 2 diabetes results from severe insulin resistance coupled with a failure of b 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.
authors.affiliation: Biochemistry Department, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Enpeng
authors.initials: E
authors.lastname: Zhao
authors.forename: Mark P
authors.initials: MP
authors.lastname: Keller
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rabaglia
authors.forename: Angie T
authors.initials: AT
authors.lastname: Oler
authors.forename: Donnie S
authors.initials: DS
authors.lastname: Stapleton
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Schueler
authors.forename: Elias Chaibub
authors.initials: EC
authors.lastname: Neto
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Moon
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Wang
authors.forename: Pek Yee
authors.initials: PY
authors.lastname: Lum
authors.forename: Irena
authors.initials: I
authors.lastname: Ivanovska
authors.forename: Michele
authors.initials: M
authors.lastname: Cleary
authors.forename: Danielle
authors.initials: D
authors.lastname: Greenawalt
authors.forename: John
authors.initials: J
authors.lastname: Tsang
authors.forename: Youn Jeong
authors.initials: YJ
authors.lastname: Choi
authors.forename: Robert
authors.initials: R
authors.lastname: Kleinhanz
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Zhou
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Howard
authors.forename: Bei B
authors.initials: BB
authors.lastname: Zhang
authors.forename: Christina
authors.initials: C
authors.lastname: Kendziorski
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Brian S
authors.initials: BS
authors.lastname: Yandell
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Alan D
authors.initials: AD
authors.lastname: Attie
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs