MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells

Zhou,Yuehua; Gu,Pingqing; Shi,Weijie; Li,Jingyun; Hao,Qun; Cao,Xiaomei; Lu,Qin; Zeng,Yu

doi:10.3892/ijmm.2016.2499

MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells

Authors:
- Yuehua Zhou
- Pingqing Gu
- Weijie Shi
- Jingyun Li
- Qun Hao
- Xiaomei Cao
- Qin Lu
- Yu Zeng
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Affiliations: Department of Obstetrics and Gynecology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200036, P.R. China, Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Obstetrics and Gynecology of Xinghua People's Hospital, Xinghua, Jiangsu 225700, P.R. China, Department of Obstetrics and Gynecology, Nanjing General Hospital of PLA, Nanjing, Jiangsu 210002, P.R. China, Duman High School, Singapore 436895, Republic of Singapore
Published online on: February 22, 2016 https://doi.org/10.3892/ijmm.2016.2499
Pages: 931-938
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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