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Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs

  • Authors:
    • Koji Fujita
    • Hisakazu Iwama
    • Kyoko Oura
    • Tomoko Tadokoro
    • Kayo Hirose
    • Miwako Watanabe
    • Teppei Sakamoto
    • Akiko Katsura
    • Shima Mimura
    • Takako Nomura
    • Joji Tani
    • Hisaaki Miyoshi
    • Asahiro Morishita
    • Hirohito Yoneyama
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Takashi Himoto
    • Tsutomu Masaki
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan, Life Science Research Center, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan, Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
    Copyright: © Fujita et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1135-1140
    |
    Published online on: September 2, 2016
       https://doi.org/10.3892/ijmm.2016.2729
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Abstract

Visceral adipose tissue contributes to the pathophysiology of metabolic syndrome. Metformin has been reported to suppress lipogenesis in a murine preadipocyte cell line. However, the effect of metformin on the differentiation of human visceral adipose tissue remains unknown. MicroRNAs (miRNAs or miRs) have been suggested as therapeutic targets because of their involvement in the differentiation and maturation of fatty cells. The aim of this study was to determine whether metformin suppresses the differentiation of human preadipocytes and to identify miRNAs associated with the regulation of lipid metabolism. Human visceral preadipocytes (HPrAD-vis) were preincubated in growth media and then cultured with differentiation media containing metformin for 1 or 2 weeks. Adipogenic differentiation of the cells was assessed by Oil Red O staining, and soluble adiponectin in the culture media was measured using an enzyme-linked immunosorbent assay. Cell proliferation was assessed using a WST-8 assay, and the gene and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT‑enhancer-binding protein α (C/EBPα) was determined by RT-qPCR and western blot analysis, respectively. miRNAs were profiled using human miRNA Oligo chips after total RNA was extracted and labeled. Oil Red O staining showed that metformin suppressed the accumulation of lipid droplets in HPrAD-vis cells. The adiponectin concentration in the culture media was also decreased in metformin-treated cells. The WST-8 assay revealed no effect on proliferation or growth inhibition following metformin treatment, although metformin suppressed the expression of PPARγ and C/EBPα. miRNA profiling further revealed differences between the metformin-treated group and control HPrAD-vis cells. Thus, the findings of the present study demonstrated that metformin suppressed the differentiation of human preadipocytes in vitro and altered the miRNA profile of these cells. Thus, the miRNAs whose expression levels were altered by metformin may contribute to the observed suppression of HPrAD-vis cell differentiation.
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1 

Kaur J: A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014:9431622014.PubMed/NCBI

2 

Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Charalampidis P, Livadas S, Kollias A, Sabico SL and Chrousos GP: Visceral adiposity index is highly associated with adiponectin values and glycaemic disturbances. Eur J Clin Invest. 43:183–189. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Simmons RK, Alberti KG, Gale EA, Colagiuri S, Tuomilehto J, Qiao Q, Ramachandran A, Tajima N, Brajkovich Mirchov I, et al: The metabolic syndrome: Useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia. 53:600–605. 2010. View Article : Google Scholar

4 

O'Brien PE, MacDonald L, Anderson M, Brennan L and Brown WA: Long-term outcomes after bariatric surgery: Fifteen-year follow-up of adjustable gastric banding and a systematic review of the bariatric surgical literature. Ann Surg. 257:87–94. 2013. View Article : Google Scholar

5 

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R and Matthews DR: Management of hyperglycaemia in type 2 diabetes: A patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 55:1577–1596. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Alexandre KB, Smit AM, Gray IP and Crowther NJ: Metformin inhibits intracellular lipid accumulation in the murine pre-adipocyte cell line, 3T3-L1. Diabetes Obes Metab. 10:688–690. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Liang J, Fu M, Ciociola E, Chandalia M and Abate N: Role of ENPP1 on adipocyte maturation. PLoS One. 2:e8822007. View Article : Google Scholar : PubMed/NCBI

8 

Fernández-Hernando C, Ramírez CM, Goedeke L and Suárez Y: MicroRNAs in metabolic disease. Arterioscler Thromb Vasc Biol. 33:178–185. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Gao Y, Xue J, Li X, Jia Y and Hu J: Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells. J Pharm Pharmacol. 60:1695–1700. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R and Olson EN: Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci USA. 109:15330–15335. 2012. View Article : Google Scholar

11 

Wilson B, Liotta LA and Petricoiniii E: Dynamic protein pathway activation mapping of adipose-derived stem cell differentiation implicates novel regulators of adipocyte differentiation. Mol Cell Proteomics. 12:2522–2535. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Berg AH, Combs TP and Scherer PE: ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 13:84–89. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Kato K, Gong J, Iwama H, Kitanaka A, Tani J, Miyoshi H, Nomura K, Mimura S, Kobayashi M, Aritomo Y, et al: The anti-diabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther. 11:549–560. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Fujita K, Iwama H, Sakamoto T, Okura R, Kobayashi K, Takano J, Katsura A, Tatsuta M, Maeda E, Mimura S, et al: Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo. Int J Oncol. 46:2419–2430. 2015.PubMed/NCBI

15 

Masaki T, Okada M, Tokuda M, Shiratori Y, Hatase O, Shirai M, Nishioka M and Omata M: Reduced C-terminal Src kinase (Csk) activities in hepatocellular carcinoma. Hepatology. 29:379–384. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Miyoshi H, Kato K, Iwama H, Maeda E, Sakamoto T, Fujita K, Toyota Y, Tani J, Nomura T, Mimura S, et al: Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo. Int J Oncol. 45:322–332. 2014.PubMed/NCBI

17 

Kobayashi M, Kato K, Iwama H, Fujihara S, Nishiyama N, Mimura S, Toyota Y, Nomura T, Nomura K, Tani J, et al: Antitumor effect of metformin in esophageal cancer: In vitro study. Int J Oncol. 42:517–524. 2013.

18 

Fujimori T, Kato K, Fujihara S, Iwama H, Yamashita T, Kobayashi K, Kamada H, Morishita A, Kobara H, Mori H, et al: Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies. Oncol Rep. 34:2987–2996. 2015.PubMed/NCBI

19 

Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T, Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, et al: Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. Int J Oncol. 46:2172–2180. 2015.PubMed/NCBI

20 

Kato K, Iwama H, Yamashita T, Kobayashi K, Fujihara S, Fujimori T, Kamada H, Kobara H and Masaki T: The anti-diabetic drug metformin inhibits pancreatic cancer cell proliferation in vitro and in vivo: Study of the microRNAs associated with the antitumor effect of metformin. Oncol Rep. 35:1582–1592. 2016.

21 

Fujita K, Kobara H, Mori H, Fujihara S, Chiyo T, Matsunaga T, Nishiyama N, Ayaki M, Yachida T, Morishita A, et al: Differences in miRNA expression profiles between GIST and leiomyoma in human samples acquired by submucosal tunneling biopsy. Endosc Int Open. 3:E665–E671. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Bolstad BM, Irizarry RA, Astrand M and Speed TP: A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 19:185–193. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, Bianco A and Daniele A: New insight into adiponectin role in obesity and obesity-related diseases. BioMed Res Int. 2014:6589132014. View Article : Google Scholar : PubMed/NCBI

24 

Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ and Spiegelman BM: Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 3:151–158. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Nakagami H: The mechanism of white and brown adipocyte differentiation. Diabetes Metab J. 37:85–90. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Son YH, Ka S, Kim AY and Kim JB: Regulation of adipocyte differentiation via MicroRNAs. Endocrinol Metab (Seoul). 29:122–135. 2014. View Article : Google Scholar

27 

Callegari E, Elamin BK, Sabbioni S, Gramantieri L and Negrini M: Role of microRNAs in hepatocellular carcinoma: A clinical perspective. Onco Targets Ther. 6:1167–1178. 2013.PubMed/NCBI

28 

Kerr TA, Korenblat KM and Davidson NO: MicroRNAs and liver disease. Transl Res. 157:241–252. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Gerin I, Bommer GT, McCoin CS, Sousa KM, Krishnan V and MacDougald OA: Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol Endocrinol Metab. 299:E198–E206. 2010.PubMed/NCBI

30 

Shin KK, Kim YS, Kim JY, Bae YC and Jung JS: miR-137 controls proliferation and differentiation of human adipose tissue stromal cells. Cell Physiol Biochem. 33:758–768. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Fujita K, Iwama H, Oura K, Tadokoro T, Hirose K, Watanabe M, Sakamoto T, Katsura A, Mimura S, Nomura T, Nomura T, et al: Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs. Int J Mol Med 38: 1135-1140, 2016.
APA
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M. ... Masaki, T. (2016). Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs. International Journal of Molecular Medicine, 38, 1135-1140. https://doi.org/10.3892/ijmm.2016.2729
MLA
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M., Sakamoto, T., Katsura, A., Mimura, S., Nomura, T., Tani, J., Miyoshi, H., Morishita, A., Yoneyama, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs". International Journal of Molecular Medicine 38.4 (2016): 1135-1140.
Chicago
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M., Sakamoto, T., Katsura, A., Mimura, S., Nomura, T., Tani, J., Miyoshi, H., Morishita, A., Yoneyama, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs". International Journal of Molecular Medicine 38, no. 4 (2016): 1135-1140. https://doi.org/10.3892/ijmm.2016.2729
Copy and paste a formatted citation
x
Spandidos Publications style
Fujita K, Iwama H, Oura K, Tadokoro T, Hirose K, Watanabe M, Sakamoto T, Katsura A, Mimura S, Nomura T, Nomura T, et al: Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs. Int J Mol Med 38: 1135-1140, 2016.
APA
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M. ... Masaki, T. (2016). Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs. International Journal of Molecular Medicine, 38, 1135-1140. https://doi.org/10.3892/ijmm.2016.2729
MLA
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M., Sakamoto, T., Katsura, A., Mimura, S., Nomura, T., Tani, J., Miyoshi, H., Morishita, A., Yoneyama, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs". International Journal of Molecular Medicine 38.4 (2016): 1135-1140.
Chicago
Fujita, K., Iwama, H., Oura, K., Tadokoro, T., Hirose, K., Watanabe, M., Sakamoto, T., Katsura, A., Mimura, S., Nomura, T., Tani, J., Miyoshi, H., Morishita, A., Yoneyama, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Metformin-suppressed differentiation of human visceral preadipocytes: Involvement of microRNAs". International Journal of Molecular Medicine 38, no. 4 (2016): 1135-1140. https://doi.org/10.3892/ijmm.2016.2729
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