MicroRNA-149 inhibits PARP-2 and promotes mitochondrial biogenesis via SIRT-1/PGC-1α network in skeletal muscle

Junaith Mohamed, Ameena Hajira, Patricia S. Pardo, Aladin M. Boriek

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

High-fat diet (HFD) plays a central role in the initiation of mitochondrial dysfunction that significantly contributes to skeletal muscle metabolic disorders in obesity. However, the mechanism by which HFD weakens skeletal muscle metabolism by altering mitochondrial function and biogenesis is unknown. Given the emerging roles of microRNAs (miRNAs) in the regulation of skeletal muscle metabolism, we sought to determine whether activation of a specific miRNA pathway would rescue the HFD-induced mitochondrial dysfunction via the sirtuin-1 (SIRT-1)/ peroxisome proliferator- activated receptor γ coactivator-1α (PGC-1α) pathway, a pathway that governs genes necessary for mitochondrial function. We here report that miR-149 strongly controls SIRT-1 expression and activity. Interestingly, miR-149 inhibits poly(ADP-ribose) polymerase-2 (PARP-2) and so increased cellular NAD+ levels and SIRT-1 activity that subsequently increases mitochondrial function and biogenesis via PGC-1α activation. In addition, skeletal muscles from HFD-fed obese mice exhibit low levels of miR-149 and high levels of PARP-2, and they show reduced mitochondrial function and biogenesis due to a decreased activation of the SIRT-1/PGC-1α pathway, suggesting that mitochondrial dysfunction in the skeletal muscle of obese mice may be because of, at least in part, miR-149 dysregulation. Overall, miR-149 may be therapeutically useful for treating HFD-induced skeletal muscle metabolic disorders in such pathophysiological conditions as obesity and type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1546-1559
Number of pages14
JournalDiabetes
Volume63
Issue number5
DOIs
StatePublished - Jan 1 2014

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Sirtuin 1
Poly(ADP-ribose) Polymerases
Organelle Biogenesis
MicroRNAs
High Fat Diet
Skeletal Muscle
Obese Mice
Muscular Diseases
Obesity
Peroxisome Proliferator-Activated Receptors
Mitochondrial Genes
NAD
Type 2 Diabetes Mellitus

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

MicroRNA-149 inhibits PARP-2 and promotes mitochondrial biogenesis via SIRT-1/PGC-1α network in skeletal muscle. / Mohamed, Junaith; Hajira, Ameena; Pardo, Patricia S.; Boriek, Aladin M.

In: Diabetes, Vol. 63, No. 5, 01.01.2014, p. 1546-1559.

Research output: Contribution to journalArticle

Mohamed, Junaith ; Hajira, Ameena ; Pardo, Patricia S. ; Boriek, Aladin M. / MicroRNA-149 inhibits PARP-2 and promotes mitochondrial biogenesis via SIRT-1/PGC-1α network in skeletal muscle. In: Diabetes. 2014 ; Vol. 63, No. 5. pp. 1546-1559.
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