Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-11T07:41:33.517Z Has data issue: false hasContentIssue false

Differential expression of cyclin G2, cyclin-dependent kinase inhibitor 2C and peripheral myelin protein 22 genes during adipogenesis

Published online by Cambridge University Press:  17 April 2014

J. Zhang
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
Y. Suh
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
Y. M. Choi
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
J. Ahn
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, OH 43210, USA
M. E. Davis
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
K. Lee*
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, OH 43210, USA
*
E-mail: Lee.2626@osu.edu
Get access

Abstract

Increase of fat cells (FCs) in adipose tissue is attributed to proliferation of preadipocytes or immature adipocytes in the early stage, as well as adipogenic differentiation in the later stage of adipose development. Although both events are involved in the FC increase, they are contrary to each other, because the former requires cell cycle activity, whereas the latter requires cell cycle withdrawal. Therefore, appropriate regulation of cell cycle inhibition is critical to adipogenesis. In order to explore the important cell cycle inhibitors and study their expression in adipogenesis, we adopted a strategy combining the Gene Expression Omnibus (GEO) database available on the NCBI website and the results of quantitative real-time PCR (qPCR) data in porcine adipose tissue. Three cell cycle inhibitors – cyclin G2 (CCNG2), cyclin-dependent kinase inhibitor 2C (CDKN2C) and peripheral myelin protein (PMP22) – were selected for study because they are relatively highly expressed in adipose tissue compared with muscle, heart, lung, liver and kidney in humans and mice based on two GEO DataSets (GDS596 and GDS3142). In the latter analysis, they were found to be more highly expressed in differentiating/ed preadipocytes than in undifferentiated preadipocytes in human and mice as shown respectively by GDS2366 and GDS2743. In addition, GDS2659 also suggested increasing expression of the three cell cycle inhibitors during differentiation of 3T3-L1 cells. Further study with qPCR in Landrace pigs did not confirm the high expression of these genes in adipose tissue compared with other tissues in market-age pigs, but confirmed higher expression of these genes in FCs than in the stromal vascular fraction, as well as increasing expression of these genes during in vitro adipogenic differentiation and in vivo development of adipose tissue. Moreover, the relatively high expression of CCNG2 in adipose tissue of market-age pigs and increasing expression during development of adipose tissue was also confirmed at the protein level by western blot analysis. Based on the analysis of the GEO DataSets and results of qPCR and Western blotting we conclude that all three cell cycle inhibitors may inhibit adipocyte proliferation, but promote adipocyte differentiation and hold a differentiated state by inducing and maintaining cell cycle inhibition. Therefore, their expression in adipose tissue is positively correlated with age and mature FC number. By regulating the expression of these genes, we may be able to control FC number, and, thus, reduce excessive fat tissue in animals and humans.

Type
Full Paper
Copyright
© The Animal Consortium 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aguilar, V, Annicotte, JS, Escote, X, Vendrell, J, Langin, D and Fajas, L 2010. Cyclin G2 regulates adipogenesis through PPARγ coactivation. Endocrinology 151, 52475254.Google Scholar
Ahn, J, Oh, SA, Suh, Y, Moeller, SJ and Lee, K 2013. Porcine G0/G1 switch gene 2 (G0S2) expression is regulated during adipogenesis and short-term in-vivo nutritional interventions. Lipids 48, 209218.Google Scholar
Albrecht, JH, Poon, RY, Ahonen, CL, Rieland, BM, Deng, C and Crary, GS 1998. Involvement of p21 and p27 in the regulation of CDK activity and cell cycle progression in the regenerating liver. Oncogene 16, 21412150.Google Scholar
Altiok, S, Xu, M and Spiegelman, BM 1997. PPARγ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes & Development 11, 19871998.Google Scholar
Anderson, DB and Kauffman, RG 1973. Cellular and enzymatic changes in porcine adipose tissue during growth. Journal of Lipid Research 14, 160168.Google Scholar
Chen, PL, Riley, DJ, Chen, Y and Lee, WH 1996. Retinoblastoma protein positively regulates terminal differentiation through direct interaction with C/EBPs. Gene & Development 10, 27942804.Google Scholar
Crawford, SM, Moeller, SJ, Zerby, HN, Irvin, KM, Kuber, PS, Velleman, SG and Leeds, TD 2010. Effects of cooked temperature on pork tenderness and relationships among muscle physiology and pork quality traits in loins from Landrace and Berkshire swine. Meat Science 84, 607612.Google Scholar
Deiuliis, JA, Li, B, Lyvers-Peffer, PA, Moeller, SJ and Lee, K 2006. Alternative splicing of delta-like 1 homolog (DLK1) in the pig and human. Comparative Biochemistry Physiology Part B 145, 5059.Google Scholar
Deiuliis, JA, Shin, J, Bae, D, Azain, MJ, Barb, R and Lee, K 2008. Developmental, hormonal, and nutritional regulation of porcine adipose triglyceride lipase (ATGL). Lipids 43, 215225.Google Scholar
Desnoyers, F, Pascal, G, Etienne, M and Vodovar, N 1980. Cellularity of adipose tissue in fetal pig. Journal of Lipid Research 21, 301308.Google Scholar
Fajas, L, Fruchart, JC and Auwerx, J 1998. Transcriptional control of adipogenesis. Current Opinion in Cell Biology 10, 165173.Google Scholar
Faust, IM, Johnson, PR, Stern, JS and Hirsch, J 1978. Diet-induced adipocyte number increase in adult rats: a new model of obesity. American Journal of Physiology 235, E279E286.Google ScholarPubMed
Guo, L, Sun, B, Shang, Z, Leng, L, Wang, Y, Wang, N and Li, H 2011. Comparison of adipose tissue cellularity in chicken ines divergently selected for fatness. Poultry Science 90, 20242034.Google Scholar
Hanamoto, T, Kajita, K, Mori, I, Ikeda, T, Fujioka, K, Yamauchi, M, Okada, H, Usui, T, Takahashi, N, Kitada, Y, Taguchi, K, Kajita, T, Uno, Y, Morita, H and Ishizuka, T 2013. The role of small proliferative adipocytes in the development of obesity: comparison between Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-obese Lon-Evans Tokushima Otsuka (LETO) rats. Endocrine Journal 60, 10011011.Google Scholar
Hausman, DB, DiGirolamo, M, Bartness, TJ, Hausman, GJ and Martin, RJ 2001. The biology of white adipocyte proliferation. Obesity Reviews 2, 239254.Google Scholar
Hirai, H, Roussel, MF, Kato, JY, Ashmun, RA and Sherr, CJ 1995. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Molecular and Cellular Biology 15, 26722681.Google Scholar
Hirsch, J and Knittle, JL 1970. Cellularity of obese and nonobese human adipose tissue. Federation Proceedings 29, 15161521.Google ScholarPubMed
Hou, CC, Feng, M, Wang, Kui and Yang, XG 2013. Lanthanides inhibit adipogenesis with promotion of cell proliferation in 3T3-L1 preadipocytes. Metallomics 5, 715722.Google Scholar
Johnson, PR and Hirsch, J 1972. Cellularity of adipose depots in six strains of genetically obese mice. The Journal of Lipid Research 13, 211.Google Scholar
Karlsson, C, Afrakhte, M, Westermark, B and Paulsson, Y 1999. Elevated level of gas3 gene expression is correlated with G0 growth arrest in human fibroblasts. Cell Biology International 23, 351358.CrossRefGoogle ScholarPubMed
Knittle, JL, Timmers, K, Ginsberg-Fellner, F, Brown, RE and Katz, DP 1979. The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. Journal of Clinical Investigation 63, 239246.Google Scholar
Li, B, Zerby, HN and Lee, K 2007. Heart fatty acid binding protein is upregulated during porcine adipocyte development. Journal of Animal Science 85, 16511659.Google Scholar
Li, B, Shin, J and Lee, K 2009. Interferon-stimulated gene ISG12b1 inhibits adipogenic differentiation and mitochondrial biogenesis in 3T3-L1 cells. Endocrinology 150, 12171224.Google Scholar
Li, X, Suh, Y, Kim, E, Moeller, SJ and Lee, K 2012. Alternative splicing and development and hormonal regulation of porcine comparative gene identification-58 (CGI-58) mRNA. Journal of Animal Science 90, 43464354.Google Scholar
Louis-Brennetot, C, Coindre, JM, Ferreira, C, Perot, G, Terrier, P and Aurias, A 2011. The CDKN2A/CDKN2B/CDK4/CCND1 pathway is pivotal in well-differentiated and dedifferentiated liposarcoma oncogenesis: an analysis of 104 tumors. Genes Chromosomes Cancer 50, 896907.Google Scholar
Manfioletti, G, Ruaro, ME, Del-Sal, G, Philipson, L and Schneider, C 1990. A growth arrest-specific (gas) gene codes for a membrane protein. Molecular and Cellular Biology 10, 29242930.Google Scholar
Morrison, RF and Farmer, SR 1999. Role of PPARγ in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. The Journal of Biological Chemistry 274, 1708817097.Google Scholar
Ntambi, JM and Kim, YC 2000. Adipocyte differentiation and gene expression. The Journal of Nutrition 130, 3122531265.Google Scholar
Re, FC, Manenti, G, Borrello, MG, Colombo, MP, Fisher, JH, Pierotti, MA, Della, PG and Dragani, TA 1992. Multiple molecular alterations in mouse lung tumors. Molecular Carcinogenesis 5, 155160.Google Scholar
Richon, VM, Lyle, RE and McGehee, RE 1997. Regulation and expression of retinoblastoma proteins p107 and p130 during 3T3-L1 adipocyte differentiation. The Journal of Biological Chemistry 272, 1011710124.CrossRefGoogle ScholarPubMed
Schafer, KA 1998. The cell cycle: a review. Veterinary Pathology 35, 461478.CrossRefGoogle ScholarPubMed
Singer, S, Socci, ND, Ambrosini, G, Sambol, E, Decarolis, P, Wu, Y, O’Connor, R, Maki, R, Viale, A, Sander, C, Schwartz, GK and Antonescu, CR 2007. Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Research 67, 66266636.CrossRefGoogle ScholarPubMed
Smas, CM and Sul, HS 1993. Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell 73, 725734.Google Scholar
Song, Y, Ahn, J, Suh, Y, Davis, ME and Lee, K 2013. Identification of novel tissue-specific genes by analysis of microarray databases: a human and mouse model. PLoS One 8, e64483.Google Scholar
Tontonoz, P, Singer, S, Forman, BM, Sarraf, P, Fletcher, JA, Fletch, CDM, Brun, RP, Mueller, E, Altiok, S, Oppenheim, H, Evans, RM and Spiegelman, BM 1997. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and retinoid X receptor. Proceedings of the National Academy of Sciences of the United States of America 94, 237241.CrossRefGoogle ScholarPubMed
Welcher, AA, Suter, U, De-Leon, M, Snipes, GJ and Shooter, EM 1991. A myelin protein is encoded by the homologue of a growth arrest-specific gene. Proceedings of the National Academy of Sciences of the United States of America 88, 71957199.Google Scholar
Zoidl, G, Blass-Kampmann, S, D’Urso, D, Schmalenbach, C and Müller, HW 1995. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. The EMBO Journal 14, 11221128.CrossRefGoogle ScholarPubMed