title: MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells.
abstract: Intrauterine growth retardation (IUGR) induces metabolic syndrome, which is often characterized by insulin resistance (IR), in adults. Previous research has shown that microRNAs (miRNAs or miRs) play a role in the target genes involved in this process, but the mechanisms remain unclear. In the present study, we examined miRNA profiles using samples of skeletal muscles from both IUGR and control rat offspring whose mothers were fed either a protein-restricted diet or a diet which involved normal amounts of protein during pregnancy, respectively. miR‑29a was found to be upregulated in the skeletal muscles of IUGR offspring. The luciferase reporter assay conﬁrmed the direct interaction between miR‑29a and peroxisome proliferator‑activated receptor δ (PPARδ). Overexpression of miR‑29a in the skeletal muscle cell line C2C12 suppressed the expression of its target gene PPARδ, which, in turn, influenced the expression of its coactivator, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Thus, PPARδ/PGC-1α‑dependent signals together reduced insulin-dependent glucose uptake and adenosine triphosphate (ATP) production. Overexpression of miR‑29a also caused a decrease in levels of glucose transporter 4 (GLUT4), the most important glucose transporter in skeletal muscle, which partially induced a decrease insulin‑dependent glucose uptake. These findings provide evidence for a novel micro-RNA‑mediated mechanism of PPARδ regulation, and we also noted the IR-promoting actions of miR-29a in skeletal muscles of IUGR.
authors.affiliation: Department of Obstetrics and Gynecology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200036, P.R. China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Pingqing
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology of Xinghua People's Hospital, Xinghua, Jiangsu 225700, P.R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing General Hospital of PLA, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Duman High School, Singapore 436895, Republic of Singapore.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Obstetrics and Gynecology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200036, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005786:Gene Expression Regulation; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007333:Insulin Resistance; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051275:Glucose Transporter Type 4; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D047494:PPAR delta; D005947:Glucose