Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice.
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.
Zhao
Enpeng
E
Biochemistry Department, University of Wisconsin, Madison, WI 53706, USA.
Keller
Mark P
MP
Rabaglia
Mary E
ME
Oler
Angie T
AT
Stapleton
Donnie S
DS
Schueler
Kathryn L
KL
Neto
Elias Chaibub
EC
Moon
Jee Young
JY
Wang
Ping
P
Wang
I-Ming
IM
Lum
Pek Yee
PY
Ivanovska
Irena
I
Cleary
Michele
M
Greenawalt
Danielle
D
Tsang
John
J
Choi
Youn Jeong
YJ
Kleinhanz
Robert
R
Shang
Jin
J
Zhou
Yun-Ping
YP
Howard
Andrew D
AD
Zhang
Bei B
BB
Kendziorski
Christina
C
Thornberry
Nancy A
NA
Yandell
Brian S
BS
Schadt
Eric E
EE
Attie
Alan D
AD
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
D035683:MicroRNAs