Endocrinol Metab.  2014 Jun;29(2):122-135. 10.3803/EnM.2014.29.2.122.

Regulation of Adipocyte Differentiation via MicroRNAs

Affiliations
  • 1Seoul National University School of Biological Sciences, Seoul National University, Seoul, Korea. jaebkim@snu.ac.kr
  • 2Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.

Abstract

Adipocyte differentiation, termed adipogenesis, is a complicated process in which pluripotent mesenchymal stem cells differentiate into mature adipocytes. The process of adipocyte differentiation is tightly regulated by a number of transcription factors, hormones and signaling pathway molecules. Recent studies have demonstrated that microRNAs, which belong to small noncoding RNA species, are also involved in adipocyte differentiation. In vivo and in vitro studies have revealed that various microRNAs affect adipogenesis by targeting several adipogenic transcription factors and key signaling molecules. In this review, we will summarize the roles of microRNAs in adipogenesis and their target genes associated with each stage of adipocyte differentiation.

Keyword

MicroRNAs; Adipocyte differentiation; Obesity

MeSH Terms

Adipocytes*
Adipogenesis
Mesenchymal Stromal Cells
MicroRNAs*
Obesity
RNA, Small Untranslated
Transcription Factors
MicroRNAs
RNA, Small Untranslated
Transcription Factors

Figure

  • Fig. 1 Signals and microRNAs involved in adipogenesis. HMGA2, high mobility group AT-hook2; CREB, cAMP response element-binding; MAPK, mitogen-activated protein kinase; WNT, wingless and INT-1; TGF-β, transforming growth factor β; TGFBR, TGF-β receptor; IRS, insulin receptor substrate; PHB, prohibitin; SMAD3, Sma and Mad related protein 3; cAMP, cyclic adenosine monophosphate; PTEN, phosphatase and tensin homolog gene; PI3K, phosphoinositide 3-kinase; ERK, extracellular signal-regulated kinase; PKA, protein kinase A; PKB, protein kinase B; KLF, Kruppel-like factor; PPAR, peroxisome proliferator-activated receptor; TCF, T-cell-specific transcription factor; LEF, lymphoid-enhancer-binding factor; C/EBP, CCAAT/enhancer-binding protein; FOXO, forkhead box protein O; SIRT1, sirtuin 1; FABP4, fatty acid binding protein 4; GLUT4, glucose transporter type 4; ADIPOQ, adiponectin; AGPAT2, 1-acyl-sn-gylcerol-3-phosphate acyltransferase beta; PEPCK, phosphoenolpyruvate carboxykinase; LPL, lipoprotein lipase.

  • Fig. 2 Regulation of osteogenesis by microRNA (miR)-27a and miR-130a. (A) Experimental scheme. primary bone marrow cell (PBMCs) were isolated from the femur and tibia of 4-week-old C56BL/6J mice. After 7 days, PBMCs were infected with retrovirus containing mock, full-length of pri-miR-27a or pri-miR-130a. Retrovirus-infected PBMCs were selected with puromycin for 5 days and differentiated for an additional 7 days. For osteoblast differentiation, PBMCs were cultured in α-modified essential medium with 10% fetal bovine serum, 50 µM ascorbic acid, and 10 mM β-glycerophosphate. All experiments with mice were approved by the Institute of Laboratory Animal Resources at Seoul National University. (B) Overexpression of miR-27a or miR-130a. The relative amounts of pri-miR-27a and pri-miR-130a against cyclophilin were measured with quantitative reverse transcription polymerase chain reaction (q-RT-PCR). Results are expressed as mean±standard error of mean (SEM). (C) Microscopic view of differentiated PBMCs after alkaline phosphatase (ALP) staining. Differentiated osteoblasts were monitored by ALP staining to reveal ALP-positive cells. (D) Expression of osteogenic marker genes. The relative mRNA levels of osteocalcin and osteopontin were measured by q-RT-PCR. Results are expressed as mean±SEM.


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