Obesity‑associated miR‑148a is regulated by cytokines and adipokines via a transcriptional mechanism

Shi,Chunmei; Pang,Lingxia; Ji,Chenbo; Wang,Jiaqin; Lin,Ning; Chen,Jiantao; Chen,Ling; Yang,Lei; Huang,Fangyan; Zhou,Yahui; Guo,Xirong; Liang,Hui; Zhang,Min

doi:10.3892/mmr.2016.5940

Obesity‑associated miR‑148a is regulated by cytokines and adipokines via a transcriptional mechanism

Authors:
- Chunmei Shi
- Lingxia Pang
- Chenbo Ji
- Jiaqin Wang
- Ning Lin
- Jiantao Chen
- Ling Chen
- Lei Yang
- Fangyan Huang
- Yahui Zhou
- Xirong Guo
- Hui Liang
- Min Zhang
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Affiliations: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pediatrics, The Third Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan 453003, P.R. China, Department of Clinical Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: November 14, 2016 https://doi.org/10.3892/mmr.2016.5940
Pages: 5707-5712

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Abstract

Our previous study revealed that miR‑148a, a cyclic adenosine monophosphate‑response element binding protein‑modulated microRNA that promotes adipocyte differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects and a mouse model. The present study investigated the expression of miR‑148a in human adipose tissue‑derived mesenchymal stem cells (hMSCs‑Ad) in response to inflammatory cytokines and adipokines to clarify its underlying mechanism. miR‑148a expression was detected using reverse transcription‑quantitative polymerase chain reaction analysis and its promoter activity was detected with a luciferase assay. miR‑148a expression levels decreased when differentiated hMSCs‑Ad were exposed to inflammatory cytokines or adipokines, which suggested that miR‑148a may be important in adipocyte metabolism and inflammation. Furthermore, the promoter activity of miR‑148a decreased following treatment of cells with inflammatory cytokines or adipokines. The results of the present study indicated a novel role of miR‑148a in adipocyte inflammation; therefore, miR‑148a may be involved in obesity complications via its own underlying transcriptional mechanism.

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1	Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK and Flegal KM: Trends in obesity prevalence among children and adolescents in the United States, 1988–1994 Through 2013–2014. JAMA. 21:2292–2299. 2016. View Article : Google Scholar
2	Glass CK and Olefsky JM: Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 15:635–645. 2012. View Article : Google Scholar : PubMed/NCBI
3	Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM and Neels JG: Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 8:301–309. 2008. View Article : Google Scholar : PubMed/NCBI
4	Ye J and McGuinness OP: Inflammation during obesity is not all bad: Evidence from animal and human studies. Am J Physiol Endocrinol Metab. 304:E466–E477. 2013. View Article : Google Scholar : PubMed/NCBI
5	Osborn O and Olefsky JM: The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 18:363–374. 2012. View Article : Google Scholar : PubMed/NCBI
6	Romeo GR, Lee J and Shoelson SE: Metabolic syndrome, insulin resistance, and roles of inflammation-mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol. 32:1771–1776. 2012. View Article : Google Scholar : PubMed/NCBI
7	Kern PA, Ranganathan S, Li C, Wood L and Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 280:E745–E751. 2001.PubMed/NCBI
8	Xu G, Zhang Y, Zhang L, Ren G and Shi Y: The role of IL-6 in inhibition of lymphocyte apoptosis by mesenchymal stem cells. Biochem Biophys Res Commun. 361:745–750. 2007. View Article : Google Scholar : PubMed/NCBI
9	Djouad F, Charbonnier LM, Bouffi C, Louis-Plence P, Bony C, Apparailly F, Cantos C, Jorgensen C and Noël D: Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells. 25:2025–2032. 2007. View Article : Google Scholar : PubMed/NCBI
10	Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC and Shi Y: Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2:141–150. 2008. View Article : Google Scholar : PubMed/NCBI
11	Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, et al: A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 105:13556–13561. 2008. View Article : Google Scholar : PubMed/NCBI
12	Shi C, Zhang M, Tong M, Yang L, Pang L, Chen L, Xu G, Chi X, Hong Q, Ni Y, et al: miR-148a is associated with obesity and modulates adipocyte differentiation of mesenchymal stem cells through Wnt signaling. Sci Rep. 5:99302015. View Article : Google Scholar : PubMed/NCBI
13	Londoño Gentile T, Lu C, Lodato PM, Tse S, Olejniczak SH, Witze ES, Thompson CB and Wellen KE: DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation. Mol Cell Biol. 33:3864–3878. 2013. View Article : Google Scholar : PubMed/NCBI
14	Braconi C, Huang N and Patel T: MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology. 51:881–890. 2010.PubMed/NCBI
15	Wellen KE, Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F and Hotamisligil GS: Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell. 129:537–548. 2007. View Article : Google Scholar : PubMed/NCBI
16	Kralisch S, Klein J, Lossner U, Bluher M, Paschke R, Stumvoll M and Fasshauer M: Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 289:E586–E590. 2005. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, et al: A deep investigation into the adipogenesis mechanism: Profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics. 11:3202010. View Article : Google Scholar : PubMed/NCBI
19	Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS and Lazar MA: The hormone resistin links obesity to diabetes. Nature. 409:307–312. 2001. View Article : Google Scholar : PubMed/NCBI
20	Kim KH, Lee K, Moon YS and Sul HS: A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem. 276:11252–11256. 2001. View Article : Google Scholar : PubMed/NCBI
21	Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R and Ranganathan S: Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1:1155–1161. 1995. View Article : Google Scholar : PubMed/NCBI
22	Jones SA: Directing transition from innate to acquired immunity: Defining a role for IL-6. J Immunol. 175:3463–3468. 2005. View Article : Google Scholar : PubMed/NCBI
23	Sethi JK and Hotamisligil GS: The role of TNF alpha in adipocyte metabolism. Semin Cell Dev Biol. 10:19–29. 1999. View Article : Google Scholar : PubMed/NCBI
24	Wernstedt Asterholm I, Tao C, Morley TS, Wang QA, Delgado-Lopez F, Wang ZV and Scherer PE: Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab. 20:103–118. 2014. View Article : Google Scholar : PubMed/NCBI
25	Lumeng CN and Saltiel AR: Inflammatory links between obesity and metabolic disease. J Clin Invest. 121:2111–2117. 2011. View Article : Google Scholar : PubMed/NCBI