Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways
Abstract
1. Introduction
2. Adipocyte Tissue Progenitors
3. The Adipocyte Formation Process (Adipogenesis)
4. Regulation of Adipogenesis Via Signalling Pathways
4.1. Insulin-Like Growth Factor 1 (IGF-1) Signalling
4.2. Glucocorticoid (GC) Signalling
4.3. cAMP Signalling
4.4. TGF-β Signalling
4.5. BMP Signalling
4.6. Wnt Signalling Pathway
4.7. Hedgehog Signalling Pathway
4.8. MAPK Signalling Pathways
4.9. Other Signalling Pathways
5. Epigenetic Regulation of Adipogenesis
5.1. Chromatin Remodelling Complexes
5.2. Histone Methylation
5.3. Histone Acetylation
5.4. Histone Deacetylation
5.5. DNA Methylation
5.6. DNA Demethylation
5.7. miRNAs
6. Transcriptional Regulation of Adipogenesis
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- World Health Organization. Obesity and Overweight. WHO Newsroom Fact Sheets: 2020. Available online: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed on 1 April 2020).
- Schmidt, F.M.; Weschenfelder, J.; Sander, C.; Minkwitz, J.; Thormann, J.; Chittka, T.; Mergl, R.; Kirkby, K.C.; Fasshauer, M.; Stumvoll, M.; et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS ONE 2015, 10, e0121971. [Google Scholar] [CrossRef] [PubMed]
- Finer, N. Medical consequences of obesity. Medicine 2015, 43, 88–93. [Google Scholar] [CrossRef]
- Hruby, A.; Hu, F.B. The Epidemiology of Obesity: A Big Picture. PharmacoEconomics 2015, 33, 673–689. [Google Scholar] [CrossRef] [PubMed]
- Zaiou, M.; El Amri, H.; Bakillah, A. The clinical potential of adipogenesis and obesity-related microRNAs. Nutr. Metab. Cardiovasc. Dis. NMCD 2018, 28, 91–111. [Google Scholar] [CrossRef] [PubMed]
- Karam, J.; McFarlane, S. Secondary causes of obesity. Therapy 2007, 4, 641–650. [Google Scholar] [CrossRef]
- De Ferranti, S.; Mozaffarian, D. The perfect storm: Obesity, adipocyte dysfunction, and metabolic consequences. Clin. Chem. 2008, 54, 945–955. [Google Scholar] [CrossRef]
- Moseti, D.; Regassa, A.; Kim, W.K. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int. J. Mol. Sci. 2016, 17, 124. [Google Scholar] [CrossRef]
- Mancuso, P. The role of adipokines in chronic inflammation. Immuno Targets Ther. 2016, 5, 47–56. [Google Scholar] [CrossRef]
- Cannon, B.; Nedergaard, J. Brown adipose tissue: Function and physiological significance. Physiol. Rev. 2004, 84, 277–359. [Google Scholar] [CrossRef]
- Labbe, S.M.; Caron, A.; Bakan, I.; Laplante, M.; Carpentier, A.C.; Lecomte, R.; Richard, D. In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis. FASEB J. 2015, 29, 2046–2058. [Google Scholar] [CrossRef]
- Hansen, I.R.; Jansson, K.M.; Cannon, B.; Nedergaard, J. Contrasting effects of cold acclimation versus obesogenic diets on chemerin gene expression in brown and brite adipose tissues. Biochim. Biophys. Acta 2014, 1841, 1691–1699. [Google Scholar] [CrossRef] [PubMed]
- Villarroya, J.; Cereijo, R.; Villarroya, F. An endocrine role for brown adipose tissue? Am. J. Physiol. Endocrinol. Metab. 2013, 305, E567–E572. [Google Scholar] [CrossRef] [PubMed]
- De Jong, J.M.; Larsson, O.; Cannon, B.; Nedergaard, J. A stringent validation of mouse adipose tissue identity markers. Am. J. Physiol. Endocrinol. Metab. 2015, 308, E1085–E1105. [Google Scholar] [CrossRef] [PubMed]
- Nedergaard, J.; Bengtsson, T.; Cannon, B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 2007, 293, E444–E452. [Google Scholar] [CrossRef]
- Sanchez-Gurmaches, J.; Hung, C.M.; Guertin, D.A. Emerging Complexities in Adipocyte Origins and Identity. Trends Cell Biol. 2016, 26, 313–326. [Google Scholar] [CrossRef]
- Pischon, T.; Boeing, H.; Hoffmann, K.; Bergmann, M.; Schulze, M.B.; Overvad, K.; van der Schouw, Y.T.; Spencer, E.; Moons, K.G.; Tjonneland., A.; et al. General and abdominal adiposity and risk of death in Europe. N. Engl. J. Med. 2008, 359, 2105–2120. [Google Scholar] [CrossRef]
- Cousin, B.; Cinti, S.; Morroni, M.; Raimbault, S.; Ricquier, D.; Penicaud, L.; Casteilla, L. Occurrence of brown adipocytes in rat white adipose tissue: Molecular and morphological characterization. J. Cell Sci. 1992, 103, 931–942. [Google Scholar]
- Nedergaard, J.; Cannon, B. The browning of white adipose tissue: Some burning issues. Cell Metab. 2014, 20, 396–407. [Google Scholar] [CrossRef]
- Poissonnet, C.M.; Burdi, A.R.; Garn, S.M. The chronology of adipose tissue appearance and distribution in the human fetus. Early Hum. Dev. 1984, 10, 1–11. [Google Scholar] [CrossRef]
- Majka, S.M.; Fox, K.E.; Psilas, J.C.; Helm, K.M.; Childs, C.R.; Acosta, A.S.; Janssen, R.C.; Friedman, J.E.; Woessner, B.T.; Shade, T.R.; et al. De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proc. Natl. Acad. Sci. USA 2010, 107, 14781–14786. [Google Scholar] [CrossRef]
- Sgaier, S.K.; Millet, S.; Villanueva, M.P.; Berenshteyn, F.; Song, C.; Joyner, A.L. Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping. Neuron 2005, 45, 27–40. [Google Scholar] [CrossRef] [PubMed]
- Timmons, J.A.; Wennmalm, K.; Larsson, O.; Walden, T.B.; Lassmann, T.; Petrovic, N.; Hamilton, D.L.; Gimeno, R.E.; Wahlestedt, C.; Baar, K.; et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc. Natl. Acad. Sci. USA 2007, 104, 4401–4406. [Google Scholar] [CrossRef] [PubMed]
- Seale, P.; Bjork, B.; Yang, W.; Kajimura, S.; Chin, S.; Kuang, S.; Scime, A.; Devarakonda, S.; Conroe, H.M.; Erdjument-Bromage, H.; et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008, 454, 961–967. [Google Scholar] [CrossRef] [PubMed]
- Lepper, C.; Fan, C.M. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis (New York: 2000) 2010, 48, 424–436. [Google Scholar] [CrossRef] [PubMed]
- Shan, T.; Liang, X.; Bi, P.; Zhang, P.; Liu, W.; Kuang, S. Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues. J. Lipid Res. 2013, 54, 2214–2224. [Google Scholar] [CrossRef]
- Sanchez-Gurmaches, J.; Hung, C.M.; Sparks, C.A.; Tang, Y.; Li, H.; Guertin, D.A. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab. 2012, 16, 348–362. [Google Scholar] [CrossRef]
- Muzumdar, M.D.; Tasic, B.; Miyamichi, K.; Li, L.; Luo, L. A global double-fluorescent Cre reporter mouse. Genesis (New York: 2000) 2007, 45, 593–605. [Google Scholar] [CrossRef]
- Sanchez-Gurmaches, J.; Guertin, D.A. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat. Commun. 2014, 5, 4099. [Google Scholar] [CrossRef]
- Lee, Y.H.; Petkova, A.P.; Konkar, A.A.; Granneman, J.G. Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J. Biol. 2015, 29, 286–299. [Google Scholar] [CrossRef]
- Barbatelli, G.; Murano, I.; Madsen, L.; Hao, Q.; Jimenez, M.; Kristiansen, K.; Giacobino, J.P.; De Matteis, R.; Cinti, S. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E1244–E1253. [Google Scholar] [CrossRef]
- Wu, J.; Bostrom, P.; Sparks, L.M.; Ye, L.; Choi, J.H.; Giang, A.H.; Khandekar, M.; Virtanen, K.A.; Nuutila, P.; Schaart, G.; et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012, 150, 366–376. [Google Scholar] [CrossRef] [PubMed]
- Ji, S.; Doumit, M.E.; Hill, R.A. Regulation of Adipogenesis and Key Adipogenic Gene Expression by 1, 25-Dihydroxyvitamin D in 3T3-L1 Cells. PLoS ONE 2015, 10, e0126142. [Google Scholar] [CrossRef]
- Gao, H.; Volat, F.; Sandhow, L.; Galitzky, J.; Nguyen, T.; Esteve, D.; Astrom, G.; Mejhert, N.; Ledoux, S.; Thalamas, C.; et al. CD36 Is a Marker of Human Adipocyte Progenitors with Pronounced Adipogenic and Triglyceride Accumulation Potential. Stem Cells (Dayton, Ohio) 2017, 35, 1799–1814. [Google Scholar] [CrossRef]
- Chen, Q.; Shou, P.; Zheng, C.; Jiang, M.; Cao, G.; Yang, Q.; Cao, J.; Xie, N.; Velletri, T.; Zhang, X.; et al. Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts? Cell. Death Differ. 2016, 23, 1128–1139. [Google Scholar] [CrossRef] [PubMed]
- Nic-Can, G.I.; Rodas-Junco, B.A.; Carrillo-Cocom, L.M.; Zepeda-Pedreguera, A.; Penaloza-Cuevas, R.; Aguilar-Ayala, F.J.; Rojas-Herrera, R.A. Epigenetic Regulation of Adipogenic Differentiation by Histone Lysine Demethylation. Int. J. Mol. Sci. 2019, 20, 3918. [Google Scholar] [CrossRef] [PubMed]
- MacDougald, O.A.; Lane, M.D. Transcriptional regulation of gene expression during adipocyte differentiation. Annu. Rev. Biochem. 1995, 64, 345–373. [Google Scholar] [CrossRef]
- Zhang, H.; Noohr, J.; Jensen, C.H.; Petersen, R.K.; Bachmann, E.; Teisner, B.; Larsen, L.K.; Mandrup, S.; Kristiansen, K. Insulin-like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation. J. Biol. Chem. 2003, 278, 20906–20914. [Google Scholar] [CrossRef]
- Zhu, D.; Shi, S.; Wang, H.; Liao, K. Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes. J. Cell Sci. 2009, 122, 2760–2768. [Google Scholar] [CrossRef]
- Boucher, J.; Mori, M.A.; Lee, K.Y.; Smyth, G.; Liew, C.W.; Macotela, Y.; Rourk, M.; Bluher, M.; Russell, S.J.; Kahn, C.R. Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signaling. Nat. Commun. 2012, 3, 902. [Google Scholar] [CrossRef]
- Lee, R.A.; Harris, C.A.; Wang, J.C. Glucocorticoid Receptor and Adipocyte Biology. Nucl. Recept. Res. 2018, 5. [Google Scholar] [CrossRef]
- Pantoja, C.; Huff, J.T.; Yamamoto, K.R. Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro. Mol. Biol. Cell. 2008, 19, 4032–4041. [Google Scholar] [CrossRef] [PubMed]
- Feve, B. Adipogenesis: Cellular and molecular aspects. Best Pract. Res. Clin. Endocrinol. Metab. 2005, 19, 483–499. [Google Scholar] [CrossRef]
- Wu, Z.; Bucher, N.L.; Farmer, S.R. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol. Cell. Biol. 1996, 16, 4128–4136. [Google Scholar] [CrossRef]
- Smas, C.M.; Chen, L.; Zhao, L.; Latasa, M.J.; Sul, H.S. Transcriptional repression of pref-1 by glucocorticoids promotes 3T3-L1 adipocyte differentiation. J. Biol. Chem. 1999, 274, 12632–12641. [Google Scholar] [CrossRef] [PubMed]
- Fox, K.E.; Colton, L.A.; Erickson, P.F.; Friedman, J.E.; Cha, H.C.; Keller, P.; MacDougald, O.A.; Klemm, D.J. Regulation of cyclin D1 and Wnt10b gene expression by cAMP-responsive element-binding protein during early adipogenesis involves differential promoter methylation. J. Biol. Chem. 2008, 283, 35096–35105. [Google Scholar] [CrossRef]
- Zhang, J.W.; Klemm, D.J.; Vinson, C.; Lane, M.D. Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis. J. Biol. Chem. 2004, 279, 4471–4478. [Google Scholar] [CrossRef]
- Tang, Q.Q.; Lane, M.D. Adipogenesis: From stem cell to adipocyte. Annu. Rev. Biochem. 2012, 81, 715–736. [Google Scholar] [CrossRef]
- Zhang, J.W.; Tang, Q.Q.; Vinson, C.; Lane, M.D. Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proc. Natl. Acad. Sci. USA 2004, 101, 43–47. [Google Scholar] [CrossRef] [PubMed]
- Petersen, R.K.; Madsen, L.; Pedersen, L.M.; Hallenborg, P.; Hagland, H.; Viste, K.; Doskeland, S.O.; Kristiansen, K. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol. Cell. Biol. 2008, 28, 3804–3816. [Google Scholar] [CrossRef]
- Vassaux, G.; Gaillard, D.; Ailhaud, G.; Negrel, R. Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP- and Ca(2+)-elevating agent. J. Biol. Chem. 1992, 267, 11092–11097. [Google Scholar]
- Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J. Transforming growth factor-beta inhibits CCAAT/enhancer-binding protein expression and PPARgamma activity in unloaded bone marrow stromal cells. Exp. Cell Res. 2005, 303, 138–147. [Google Scholar] [CrossRef] [PubMed]
- Li, S.-N.; Wu, J.-F. TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment. Stem Cell Res. Ther. 2020, 11, 41. [Google Scholar] [CrossRef] [PubMed]
- Abou-Ezzi, G.; Supakorndej, T.; Zhang, J.; Anthony, B.; Krambs, J.; Celik, H.; Karpova, D.; Craft, C.S.; Link, D.C. TGF-beta Signaling Plays an Essential Role in the Lineage Specification of Mesenchymal Stem/Progenitor Cells in Fetal Bone Marrow. Stem Cell Rep. 2019, 13, 48–60. [Google Scholar] [CrossRef] [PubMed]
- Elsafadi, M.; Manikandan, M.; Atteya, M.; Abu Dawud, R.; Almalki, S.; Ali Kaimkhani, Z.; Aldahmash, A.; Alajez, N.M.; Alfayez, M.; Kassem, M.; et al. SERPINB2 is a novel TGFbeta-responsive lineage fate determinant of human bone marrow stromal cells. Sci. Rep. 2017, 7, 10797. [Google Scholar] [CrossRef]
- Huang, H.; Song, T.J.; Li, X.; Hu, L.; He, Q.; Liu, M.; Lane, M.D.; Tang, Q.Q. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc. Natl. Acad. Sci. USA 2009, 106, 12670–12675. [Google Scholar] [CrossRef] [PubMed]
- Tang, Q.Q.; Otto, T.C.; Lane, M.D. Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc. Natl. Acad. Sci. USA 2004, 101, 9607–9611. [Google Scholar] [CrossRef]
- Bowers, R.R.; Kim, J.W.; Otto, T.C.; Lane, M.D. Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 gene. Proc. Natl. Acad. Sci. USA 2006, 103, 13022–13027. [Google Scholar] [CrossRef]
- Wang, E.A.; Israel, D.I.; Kelly, S.; Luxenberg, D.P. Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors (Chur. Switzerland) 1993, 9, 57–71. [Google Scholar] [CrossRef]
- Hata, K.; Nishimura, R.; Ikeda, F.; Yamashita, K.; Matsubara, T.; Nokubi, T.; Yoneda, T. Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Mol. Biol. Cell. 2003, 14, 545–555. [Google Scholar] [CrossRef]
- Elsafadi, M.; Shinwari, T.; Al-Malki, S.; Manikandan, M.; Mahmood, A.; Aldahmash, A.; Alfayez, M.; Kassem, M.; Alajez, N.M. Author Correction: Convergence of TGFbeta and BMP signaling in regulating human bone marrow stromal cell differentiation. Sci. Rep. 2019, 9, 17827. [Google Scholar] [CrossRef]
- Xue, R.; Wan, Y.; Zhang, S.; Zhang, Q.; Ye, H.; Li, Y. Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes. Am. J. Physiol. Endocrin. Metab. 2014, 306, E363–E372. [Google Scholar] [CrossRef] [PubMed]
- Elsen, M.; Raschke, S.; Tennagels, N.; Schwahn, U.; Jelenik, T.; Roden, M.; Romacho, T.; Eckel, J. BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells. Am. J. Physiol. Endocrin. Metab. 2014, 306, C431–C440. [Google Scholar] [CrossRef] [PubMed]
- Tseng, Y.H.; Kokkotou, E.; Schulz, T.J.; Huang, T.L.; Winnay, J.N.; Taniguchi, C.M.; Tran, T.T.; Suzuki, R.; Espinoza, D.O.; Yamamoto, Y.; et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008, 454, 1000–1004. [Google Scholar] [CrossRef] [PubMed]
- Laudes, M. Role of WNT signaling in the determination of human mesenchymal stem cells into preadipocytes. J. Mol. Endocrinol. 2011, 46, R65–R72. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Komiya, Y.; Habas, R. Wnt signal transduction pathways. Organogenesis 2008, 4, 68–75. [Google Scholar] [CrossRef]
- Karczewska-Kupczewska, M.; Stefanowicz, M.; Matulewicz, N.; Nikolajuk, A.; Straczkowski, M. Wnt Signaling Genes in Adipose Tissue and Skeletal Muscle of Humans With Different Degrees of Insulin Sensitivity. Am. J. Physiol. Endocrin. Metab. 2016, 101, 3079–3087. [Google Scholar] [CrossRef]
- Prestwich, T.C.; Macdougald, O.A. Wnt/beta-catenin signaling in adipogenesis and metabolism. Curr. Opin. Cell Biol. 2007, 19, 612–617. [Google Scholar] [CrossRef]
- 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/β-catenin signaling pathway. BMC Genomics 2010, 11, 320. [Google Scholar] [CrossRef]
- Bowers, R.R.; Lane, M.D. Wnt signaling and adipocyte lineage commitment. Cell Cycle 2008, 7, 1191–1196. [Google Scholar] [CrossRef]
- Chen, N.; Wang, J. Wnt/beta-Catenin Signaling and Obesity. Front. Physiol. 2018, 9, 792. [Google Scholar] [CrossRef]
- Davis, L.A.; Zur Nieden, N.I. Mesodermal fate decisions of a stem cell: The Wnt switch. Cell. Molec. Life Sci. 2008, 65, 2658–2674. [Google Scholar] [CrossRef] [PubMed]
- Lee, R.T.H.; Zhao, Z.; Ingham, P.W. Hedgehog signaling. Development (Cambridge, England) 2016, 143, 367. [Google Scholar] [CrossRef] [PubMed]
- Spinella-Jaegle, S.; Rawadi, G.; Kawai, S.; Gallea, S.; Faucheu, C.; Mollat, P.; Courtois, B.; Bergaud, B.; Ramez, V.; Blanchet, A.M.; et al. Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J. Cell Sci. 2001, 114, 2085–2094. [Google Scholar] [PubMed]
- Shi, Y.; Long, F. Hedgehog signaling via Gli2 prevents obesity induced by high-fat diet in adult mice. eLife 2017, 6. [Google Scholar] [CrossRef]
- Suh, J.M.; Gao, X.; McKay, J.; McKay, R.; Salo, Z.; Graff, J.M. Hedgehog signaling plays a conserved role in inhibiting fat formation. Cell Metab. 2006, 3, 25–34. [Google Scholar] [CrossRef]
- Aouadi, M.; Laurent, K.; Prot, M.; Le Marchand-Brustel, Y.; Binetruy, B.; Bost, F. Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes 2006, 55, 281–289. [Google Scholar] [CrossRef]
- Bost, F.; Aouadi, M.; Caron, L.; Even, P.; Belmonte, N.; Prot, M.; Dani, C.; Hofman, P.; Pages, G.; Pouyssegur, J.; et al. The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis. Diabetes 2005, 54, 402–411. [Google Scholar] [CrossRef]
- Hu, E.; Kim, J.B.; Sarraf, P.; Spiegelman, B.M. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science (New York, NY) 1996, 274, 2100–2103. [Google Scholar] [CrossRef]
- Font de Mora, J.; Porras, A.; Ahn, N.; Santos, E. Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation. Mol. Cell. Biol. 1997, 17, 6068–6075. [Google Scholar] [CrossRef] [PubMed]
- Aouadi, M.; Jager, J.; Laurent, K.; Gonzalez, T.; Cormont, M.; Binetruy, B.; Le Marchand-Brustel, Y.; Tanti, J.F.; Bost, F. p38MAP Kinase activity is required for human primary adipocyte differentiation. FEBS Lett. 2007, 581, 5591–5596. [Google Scholar] [CrossRef] [PubMed]
- Engelman, J.A.; Lisanti, M.P.; Scherer, P.E. Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J. Biol. Chem. 1998, 273, 32111–32120. [Google Scholar] [CrossRef]
- Engelman, J.A.; Berg, A.H.; Lewis, R.Y.; Lin, A.; Lisanti, M.P.; Scherer, P.E. Constitutively active mitogen-activated protein kinase kinase 6 (MKK6) or salicylate induces spontaneous 3T3-L1 adipogenesis. The J. Biol. Chem. 1999, 274, 35630–35638. [Google Scholar] [CrossRef]
- Porras, A.; Muszynski, K.; Rapp, U.R.; Santos, E. Dissociation between activation of Raf-1 kinase and the 42-kDa mitogen-activated protein kinase/90-kDa S6 kinase (MAPK/RSK) cascade in the insulin/Ras pathway of adipocytic differentiation of 3T3 L1 cells. J. Biol. Chem. 1994, 269, 12741–12748. [Google Scholar] [PubMed]
- Fajas, L.; Egler, V.; Reiter, R.; Hansen, J.; Kristiansen, K.; Debril, M.B.; Miard, S.; Auwerx, J. The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation. Dev. Cell 2002, 3, 903–910. [Google Scholar] [CrossRef]
- Tang, Q.Q.; Lane, M.D. Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation. Genes Dev. 1999, 13, 2231–2241. [Google Scholar] [CrossRef] [PubMed]
- Thomas, D.M.; Carty, S.A.; Piscopo, D.M.; Lee, J.S.; Wang, W.F.; Forrester, W.C.; Hinds, P.W. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol. Cell 2001, 8, 303–316. [Google Scholar] [CrossRef]
- Rebbapragada, A.; Benchabane, H.; Wrana, J.L.; Celeste, A.J.; Attisano, L. Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Mol. Cell. Biol. 2003, 23, 7230–7242. [Google Scholar] [CrossRef] [PubMed]
- Chen, W.; Zhu, Q.; Liu, Y.; Zhang, Q. Chromatin Remodeling and Plant Immunity. Adv. Protein Chem. Struct. Biol. 2017, 106, 243–260. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.E.; Schmidt, H.; Lai, B.; Ge, K. Transcriptional and Epigenomic Regulation of Adipogenesis. Mol. Cell. Biol. 2019, 39. [Google Scholar] [CrossRef] [PubMed]
- Salma, N.; Xiao, H.; Mueller, E.; Imbalzano, A.N. Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor. Mol. Cell. Biol. 2004, 24, 4651–4663. [Google Scholar] [CrossRef] [PubMed]
- Marino-Ramirez, L.; Kann, M.G.; Shoemaker, B.A.; Landsman, D. Histone structure and nucleosome stability. Expert Rev. Proteom. 2005, 2, 719–729. [Google Scholar] [CrossRef] [PubMed]
- Okamura, M.; Inagaki, T.; Tanaka, T.; Sakai, J. Role of histone methylation and demethylation in adipogenesis and obesity. Organogenesis 2010, 6, 24–32. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Jin, Q.; Lee, J.E.; Su, I.H.; Ge, K. Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate adipogenesis. Proc. Natl. Acad. Sci. USA 2010, 107, 7317–7322. [Google Scholar] [CrossRef]
- Musri, M.M.; Carmona, M.C.; Hanzu, F.A.; Kaliman, P.; Gomis, R.; Parrizas, M. Histone demethylase LSD1 regulates adipogenesis. J. Biol. Chem. 2010, 285, 30034–30041. [Google Scholar] [CrossRef] [PubMed]
- Musri, M.M.; Corominola, H.; Casamitjana, R.; Gomis, R.; Parrizas, M. Histone H3 lysine 4 dimethylation signals the transcriptional competence of the adiponectin promoter in preadipocytes. J. Biol. Chem. 2006, 281, 17180–17188. [Google Scholar] [CrossRef]
- Sambeat, A.; Gulyaeva, O.; Dempersmier, J.; Tharp, K.M.; Stahl, A.; Paul, S.M.; Sul, H.S. LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program. Cell Rep. 2016, 15, 2536–2549. [Google Scholar] [CrossRef]
- Wang, L.; Xu, S.; Lee, J.E.; Baldridge, A.; Grullon, S.; Peng, W.; Ge, K. Histone H3K9 methyltransferase G9a represses PPARgamma expression and adipogenesis. Embo. J. 2013, 32, 45–59. [Google Scholar] [CrossRef]
- Zhuang, L.; Jang, Y.; Park, Y.-K.; Lee, J.-E.; Jain, S.; Froimchuk, E.; Broun, A.; Liu, C.; Gavrilova, O.; Ge, K. Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function. Nat. Commun. 2018, 9, 1796. [Google Scholar] [CrossRef]
- Brier, A.B.; Loft, A.; Madsen, J.G.S.; Rosengren, T.; Nielsen, R.; Schmidt, S.F.; Liu, Z.; Yan, Q.; Gronemeyer, H.; Mandrup, S. The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation. Nucleic Acids Res. 2017, 45, 1743–1759. [Google Scholar] [CrossRef]
- Zhang, Q.; Ramlee, M.K.; Brunmeir, R.; Villanueva, C.J.; Halperin, D.; Xu, F. Dynamic and distinct histone modifications modulate the expression of key adipogenesis regulatory genes. Cell Cycle 2012, 11, 4310–4322. [Google Scholar] [CrossRef]
- Ge, K. Epigenetic regulation of adipogenesis by histone methylation. Biochim. Biophys. Acta 2012, 1819, 727–732. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.-E.; Wang, C.; Xu, S.; Cho, Y.-W.; Wang, L.; Feng, X.; Baldridge, A.; Sartorelli, V.; Zhuang, L.; Peng, W.; et al. H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. eLife 2013, 2, e01503. [Google Scholar] [CrossRef] [PubMed]
- Ohno, H.; Shinoda, K.; Ohyama, K.; Sharp, L.Z.; Kajimura, S. EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 2013, 504, 163–167. [Google Scholar] [CrossRef]
- Yadav, N.; Cheng, D.; Richard, S.; Morel, M.; Iyer, V.R.; Aldaz, C.M.; Bedford, M.T. CARM1 promotes adipocyte differentiation by coactivating PPARgamma. EMBO Rep. 2008, 9, 193–198. [Google Scholar] [CrossRef]
- LeBlanc, S.E.; Wu, Q.; Lamba, P.; Sif, S.; Imbalzano, A.N. Promoter-enhancer looping at the PPARgamma2 locus during adipogenic differentiation requires the Prmt5 methyltransferase. Nucleic Acids Res. 2016, 44, 5133–5147. [Google Scholar] [CrossRef] [PubMed]
- LeBlanc, S.E.; Konda, S.; Wu, Q.; Hu, Y.J.; Oslowski, C.M.; Sif, S.; Imbalzano, A.N. Protein arginine methyltransferase 5 (Prmt5) promotes gene expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and its target genes during adipogenesis. Mol. Endocrinol. 2012, 26, 583–597. [Google Scholar] [CrossRef]
- Jiang, Y.H.; Bressler, J.; Beaudet, A.L. Epigenetics and human disease. Annu. Rev. Genom. Hum. Genet. 2004, 5, 479–510. [Google Scholar] [CrossRef]
- Verdone, L.; Agricola, E.; Caserta, M.; Di Mauro, E. Histone acetylation in gene regulation. Brief. Funct. Genom. Proteom. 2006, 5, 209–221. [Google Scholar] [CrossRef]
- Jin, Q.; Wang, C.; Kuang, X.; Feng, X.; Sartorelli, V.; Ying, H.; Ge, K.; Dent, S.Y. Gcn5 and PCAF regulate PPARgamma and Prdm16 expression to facilitate brown adipogenesis. Mol. Cell. Biol. 2014, 34, 3746–3753. [Google Scholar] [CrossRef]
- Takahashi, N.; Kawada, T.; Yamamoto, T.; Goto, T.; Taimatsu, A.; Aoki, N.; Kawasaki, H.; Taira, K.; Yokoyama, K.K.; Kamei, Y.; et al. Overexpression and ribozyme-mediated targeting of transcriptional coactivators CREB-binding protein and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 2002, 277, 16906–16912. [Google Scholar] [CrossRef]
- Yamauchi, T.; Oike, Y.; Kamon, J.; Waki, H.; Komeda, K.; Tsuchida, A.; Date, Y.; Li, M.X.; Miki, H.; Akanuma, Y.; et al. Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Nat. Genet. 2002, 30, 221–226. [Google Scholar] [CrossRef] [PubMed]
- Xu, Z.; Ande, S.R.; Mishra, S. Temporal analysis of protein lysine acetylation during adipocyte differentiation. Adipocyte 2013, 2, 33–40. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.D.; Feldman, Z.B.; Doherty, S.P.; Reyes, J.M.; Rahl, P.B.; Lin, C.Y.; Sheng, Q.; Duan, Q.; Federation, A.J.; Kung, A.L.; et al. BET bromodomain proteins regulate enhancer function during adipogenesis. Proc. Natl. Acad. Sci. USA 2018, 115, 2144–2149. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.E.; Park, Y.K.; Park, S.; Jang, Y.; Waring, N.; Dey, A.; Ozato, K.; Lai, B.; Peng, W.; Ge, K. Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis. Nat. Commun. 2017, 8, 2217. [Google Scholar] [CrossRef]
- Rajan, A.; Shi, H.; Xue, B. Class I and II Histone Deacetylase Inhibitors Differentially Regulate Thermogenic Gene Expression in Brown Adipocytes. Sci. Rep. 2018, 8, 13072. [Google Scholar] [CrossRef]
- Yoo, E.J.; Chung, J.J.; Choe, S.S.; Kim, K.H.; Kim, J.B. Down-regulation of histone deacetylases stimulates adipocyte differentiation. J. Biol. Chem. 2006, 281, 6608–6615. [Google Scholar] [CrossRef]
- Kuzmochka, C.; Abdou, H.S.; Hache, R.J.; Atlas, E. Inactivation of histone deacetylase 1 (HDAC1) but not HDAC2 is required for the glucocorticoid-dependent CCAAT/enhancer-binding protein alpha (C/EBPalpha) expression and preadipocyte differentiation. Endocrinology 2014, 155, 4762–4773. [Google Scholar] [CrossRef]
- Haberland, M.; Carrer, M.; Mokalled, M.H.; Montgomery, R.L.; Olson, E.N. Redundant control of adipogenesis by histone deacetylases 1 and 2. J. Biol. Chem. 2010, 285, 14663–14670. [Google Scholar] [CrossRef]
- Chatterjee, T.K.; Idelman, G.; Blanco, V.; Blomkalns, A.L.; Piegore, M.G., Jr.; Weintraub, D.S.; Kumar, S.; Rajsheker, S.; Manka, D.; Rudich, S.M.; et al. Histone deacetylase 9 is a negative regulator of adipogenic differentiation. J. Biol. Chem. 2011, 286, 27836–27847. [Google Scholar] [CrossRef]
- Fang, J.; Ianni, A.; Smolka, C.; Vakhrusheva, O.; Nolte, H.; Kruger, M.; Wietelmann, A.; Simonet, N.G.; Adrian-Segarra, J.M.; Vaquero, A.; et al. Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1. Proc. Natl. Acad. Sci. USA 2017, 114, E8352–E8361. [Google Scholar] [CrossRef]
- Sanders, B.D.; Jackson, B.; Marmorstein, R. Structural basis for sirtuin function: What we know and what we don’t. Biochim. Biophys. Acta 2010, 1804, 1604–1616. [Google Scholar] [CrossRef] [PubMed]
- Picard, F.; Kurtev, M.; Chung, N.; Topark-Ngarm, A.; Senawong, T.; Machado De Oliveira, R.; Leid, M.; McBurney, M.W.; Guarente, L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004, 429, 771–776. [Google Scholar] [CrossRef] [PubMed]
- Mayoral, R.; Osborn, O.; McNelis, J.; Johnson, A.M.; Oh, D.Y.; Izquierdo, C.L.; Chung, H.; Li, P.; Traves, P.G.; Bandyopadhyay, G.; et al. Adipocyte SIRT1 knockout promotes PPARgamma activity, adipogenesis and insulin sensitivity in chronic-HFD and obesity. Mol. Metab. 2015, 4, 378–391. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Tong, Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1′s repressive interaction with PPARgamma. Mol. Biol. Cell. 2009, 20, 801–808. [Google Scholar] [CrossRef] [PubMed]
- Chen, Q.; Hao, W.; Xiao, C.; Wang, R.; Xu, X.; Lu, H.; Chen, W.; Deng, C.X. SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion. Cell Rep. 2017, 18, 3155–3166. [Google Scholar] [CrossRef]
- Moore, L.D.; Le, T.; Fan, G. DNA methylation and its basic function. Neuropsychopharmacology 2013, 38, 23–38. [Google Scholar] [CrossRef]
- Jin, B.; Li, Y.; Robertson, K.D. DNA methylation: Superior or subordinate in the epigenetic hierarchy? Genes Cancer 2011, 2, 607–617. [Google Scholar] [CrossRef]
- Londono Gentile, T.; Lu, C.; Lodato, P.M.; Tse, S.; Olejniczak, S.H.; Witze, E.S.; Thompson, C.B.; Wellen, K.E. DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation. Mol. Cell. Biol. 2013, 33, 3864–3878. [Google Scholar] [CrossRef]
- Rasmussen, K.D.; Helin, K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 2016, 30, 733–750. [Google Scholar] [CrossRef]
- Yoo, Y.; Park, J.H.; Weigel, C.; Liesenfeld, D.B.; Weichenhan, D.; Plass, C.; Seo, D.G.; Lindroth, A.M.; Park, Y.J. TET-mediated hydroxymethylcytosine at the Ppargamma locus is required for initiation of adipogenic differentiation. Int. J. Obes. (2005) 2017, 41, 652–659. [Google Scholar] [CrossRef]
- Zhou, Y.; Zhou, Z.; Zhang, W.; Hu, X.; Wei, H.; Peng, J.; Jiang, S. SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling. Cell Biosci. 2015, 5, 61. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, J.; Hayder, H.; Zayed, Y.; Peng, C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrin. 2018, 9, 402. [Google Scholar] [CrossRef]
- Hilton, C.; Neville, M.J.; Karpe, F. MicroRNAs in adipose tissue: Their role in adipogenesis and obesity. Int. J. Obes. 2013, 37, 325–332. [Google Scholar] [CrossRef] [PubMed]
- Esau, C.; Kang, X.; Peralta, E.; Hanson, E.; Marcusson, E.G.; Ravichandran, L.V.; Sun, Y.; Koo, S.; Perera, R.J.; Jain, R.; et al. MicroRNA-143 regulates adipocyte differentiation. J. Biol. Chem. 2004, 279, 52361–52365. [Google Scholar] [CrossRef] [PubMed]
- Son, Y.H.; Ka, S.; Kim, A.Y.; Kim, J.B. Regulation of Adipocyte Differentiation via MicroRNAs. Endocrinol. Metab. (Seoul, Korea) 2014, 29, 122–135. [Google Scholar] [CrossRef]
- Fang, L.L.; Wang, X.H.; Sun, B.F.; Zhang, X.D.; Zhu, X.H.; Yu, Z.J.; Luo, H. Expression, regulation and mechanism of action of the miR-17–92 cluster in tumor cells (Review). Int. J. Mol. Med. 2017, 40, 1624–1630. [Google Scholar] [CrossRef]
- Wang, Q.; Li, Y.C.; Wang, J.; Kong, J.; Qi, Y.; Quigg, R.J.; Li, X. miR-17–92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc. Natl. Acad. Sci. USA 2008, 105, 2889–2894. [Google Scholar] [CrossRef]
- Ouyang, D.; Ye, Y.; Guo, D.; Yu, X.; Chen, J.; Qi, J.; Tan, X.; Zhang, Y.; Ma, Y.; Li, Y. MicroRNA-125b-5p inhibits proliferation and promotes adipogenic differentiation in 3T3-L1 preadipocytes. Acta Biochim. Biophys. Sin. (Shanghai) 2015, 47, 355–361. [Google Scholar] [CrossRef]
- Zaragosi, L.E.; Wdziekonski, B.; Brigand, K.L.; Villageois, P.; Mari, B.; Waldmann, R.; Dani, C.; Barbry, P. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol. 2011, 12, R64. [Google Scholar] [CrossRef]
- Huang, J.; Zhao, L.; Xing, L.; Chen, D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells (Dayton, Ohio) 2010, 28, 357–364. [Google Scholar] [CrossRef]
- Lee, E.K.; Lee, M.J.; Abdelmohsen, K.; Kim, W.; Kim, M.M.; Srikantan, S.; Martindale, J.L.; Hutchison, E.R.; Kim, H.H.; Marasa, B.S.; et al. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol. Cell. Biol. 2011, 31, 626–638. [Google Scholar] [CrossRef] [PubMed]
- Lin, Q.; Gao, Z.; Alarcon, R.M.; Ye, J.; Yun, Z. A role of miR-27 in the regulation of adipogenesis. FEBS J. 2009, 276, 2348–2358. [Google Scholar] [CrossRef] [PubMed]
- Ahn, J.; Lee, H.; Jung, C.H.; Jeon, T.I.; Ha, T.Y. MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade. EMBO Mol. Med. 2013, 5, 1602–1612. [Google Scholar] [CrossRef] [PubMed]
- Cioffi, M.; Vallespinos-Serrano, M.; Trabulo, S.M.; Fernandez-Marcos, P.J.; Firment, A.N.; Vazquez, B.N.; Vieira, C.R.; Mulero, F.; Camara, J.A.; Cronin, U.P.; et al. MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3. Cell Rep. 2015, 12, 1594–1605. [Google Scholar] [CrossRef] [PubMed]
- Ambele, M.A.; Pepper, M.S. Identification of transcription factors potentially involved in human adipogenesis in vitro. Mol. Genet. Genom. Med. 2017, 5, 210–222. [Google Scholar] [CrossRef]
- Mota de Sa, P.; Richard, A.J.; Hang, H.; Stephens, J.M. Transcriptional Regulation of Adipogenesis. Compr. Physiol. 2017, 7, 635–674. [Google Scholar] [CrossRef] [PubMed]
- Longo, M.; Raciti, G.A.; Zatterale, F.; Parrillo, L.; Desiderio, A.; Spinelli, R.; Hammarstedt, A.; Hedjazifar, S.; Hoffmann, J.M.; Nigro, C.; et al. Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity. Diabetologia 2018, 61, 369–380. [Google Scholar] [CrossRef]
- Gupta, R.K.; Arany, Z.; Seale, P.; Mepani, R.J.; Ye, L.; Conroe, H.M.; Roby, Y.A.; Kulaga, H.; Reed, R.R.; Spiegelman, B.M. Transcriptional control of preadipocyte determination by Zfp423. Nature 2010, 464, 619–623. [Google Scholar] [CrossRef] [PubMed]
- Hu, X.; Zhou, Y.; Yang, Y.; Peng, J.; Song, T.; Xu, T.; Wei, H.; Jiang, S.; Peng, J. Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment. Open Biol. 2016, 6. [Google Scholar] [CrossRef] [PubMed]
- Quach, J.M.; Walker, E.C.; Allan, E.; Solano, M.; Yokoyama, A.; Kato, S.; Sims, N.A.; Gillespie, M.T.; Martin, T.J. Zinc finger protein 467 is a novel regulator of osteoblast and adipocyte commitment. J. Biol. Chem. 2011, 286, 4186–4198. [Google Scholar] [CrossRef]
- Festa, E.; Fretz, J.; Berry, R.; Schmidt, B.; Rodeheffer, M.; Horowitz, M.; Horsley, V. Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 2011, 146, 761–771. [Google Scholar] [CrossRef] [PubMed]
- Jimenez, M.A.; Akerblad, P.; Sigvardsson, M.; Rosen, E.D. Critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade. Mol. Cell. Biol. 2007, 27, 743–757. [Google Scholar] [CrossRef]
- Harp, J.B.; Franklin, D.; Vanderpuije, A.A.; Gimble, J.M. Differential expression of signal transducers and activators of transcription during human adipogenesis. Biochem. Biophys. Res. Commun. 2001, 281, 907–912. [Google Scholar] [CrossRef]
- Shang, C.A.; Waters, M.J. Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes. Mol. Endocrinol. 2003, 17, 2494–2508. [Google Scholar] [CrossRef]
- Teglund, S.; McKay, C.; Schuetz, E.; van Deursen, J.M.; Stravopodis, D.; Wang, D.; Brown, M.; Bodner, S.; Grosveld, G.; Ihle, J.N. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 1998, 93, 841–850. [Google Scholar] [CrossRef]
- Floyd, Z.E.; Stephens, J.M. STAT5A promotes adipogenesis in nonprecursor cells and associates with the glucocorticoid receptor during adipocyte differentiation. Diabetes 2003, 52, 308–314. [Google Scholar] [CrossRef] [PubMed]
- Kawai, M.; Namba, N.; Mushiake, S.; Etani, Y.; Nishimura, R.; Makishima, M.; Ozono, K. Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway. J. Mol. Endocrinol. 2007, 38, 19–34. [Google Scholar] [CrossRef]
- Stewart, W.C.; Pearcy, L.A.; Floyd, Z.E.; Stephens, J.M. STAT5A expression in Swiss 3T3 cells promotes adipogenesis in vivo in an athymic mice model system. Obesity 2011, 19, 1731–1734. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.S.; Huang, H.Y.; Chen, S.Z.; Li, X.; Zhang, W.T.; Tang, Q.Q. Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the adipocyte lineage. FEBS J. 2013, 280, 2644–2651. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.A.; Tao, C.; Jiang, L.; Shao, M.; Ye, R.; Zhu, Y.; Gordillo, R.; Ali, A.; Lian, Y.; Holland, W.L.; et al. Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation. Nat. Cell Biol. 2015, 17, 1099–1111. [Google Scholar] [CrossRef] [PubMed]
- Rosen, E.D.; Sarraf, P.; Troy, A.E.; Bradwin, G.; Moore, K.; Milstone, D.S.; Spiegelman, B.M.; Mortensen, R.M. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 1999, 4, 611–617. [Google Scholar] [CrossRef]
- Hu, E.; Tontonoz, P.; Spiegelman, B.M. Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc. Natl. Acad. Sci. USA 1995, 92, 9856–9860. [Google Scholar] [CrossRef] [PubMed]
- Rosen, E.; Eguchi, J.; Xu, Z. Transcriptional targets in adipocyte biology. Expert Opin. Ther. Targets 2009, 13, 975–986. [Google Scholar] [CrossRef]
- Escalona-Nandez, I.; Guerrero-Escalera, D.; Estanes-Hernandez, A.; Ortiz-Ortega, V.; Tovar, A.R.; Perez-Monter, C. The activation of peroxisome proliferator-activated receptor gamma is regulated by Kruppel-like transcription factors 6 & 9 under steatotic conditions. Biochem. Biophys. Res. Commun. 2015, 458, 751–756. [Google Scholar] [CrossRef]
- Hamm, J.K.; Park, B.H.; Farmer, S.R. A role for C/EBPbeta in regulating peroxisome proliferator-activated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes. J. Biol. Chem. 2001, 276, 18464–18471. [Google Scholar] [CrossRef] [PubMed]
- Otto, T.C.; Lane, M.D. Adipose development: From stem cell to adipocyte. Crit. Rev. Biochem. Mol. Biol. 2005, 40, 229–242. [Google Scholar] [CrossRef]
- Gonzalez, F.J. Getting fat: Two new players in molecular adipogenesis. Cell Metab. 2005, 1, 85–86. [Google Scholar] [CrossRef]
- Du, C.; Ma, X.; Meruvu, S.; Hugendubler, L.; Mueller, E. The adipogenic transcriptional cofactor ZNF638 interacts with splicing regulators and influences alternative splicing. J. Lipid Res. 2014, 55, 1886–1896. [Google Scholar] [CrossRef]
- Meraz, M.A.; White, J.M.; Sheehan, K.C.; Bach, E.A.; Rodig, S.J.; Dighe, A.S.; Kaplan, D.H.; Riley, J.K.; Greenlund, A.C.; Campbell, D.; et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 1996, 84, 431–442. [Google Scholar] [CrossRef]
- Birsoy, K.; Chen, Z.; Friedman, J. Transcriptional regulation of adipogenesis by KLF4. Cell Metab. 2008, 7, 339–347. [Google Scholar] [CrossRef]
- Oishi, Y.; Manabe, I.; Tobe, K.; Tsushima, K.; Shindo, T.; Fujiu, K.; Nishimura, G.; Maemura, K.; Yamauchi, T.; Kubota, N.; et al. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab. 2005, 1, 27–39. [Google Scholar] [CrossRef]
- Mori, T.; Sakaue, H.; Iguchi, H.; Gomi, H.; Okada, Y.; Takashima, Y.; Nakamura, K.; Nakamura, T.; Yamauchi, T.; Kubota, N.; et al. Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J. Biol. Chem. 2005, 280, 12867–12875. [Google Scholar] [CrossRef]
- Ambele, M.A.; Dessels, C.; Durandt, C.; Pepper, M.S. Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation. Stem Cell. Res. 2016, 16, 725–734. [Google Scholar] [CrossRef]
- Banerjee, S.S.; Feinberg, M.W.; Watanabe, M.; Gray, S.; Haspel, R.L.; Denkinger, D.J.; Kawahara, R.; Hauner, H.; Jain, M.K. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. J. Biol. Chem. 2003, 278, 2581–2584. [Google Scholar] [CrossRef] [PubMed]
- Sue, N.; Jack, B.H.; Eaton, S.A.; Pearson, R.C.; Funnell, A.P.; Turner, J.; Czolij, R.; Denyer, G.; Bao, S.; Molero-Navajas, J.C.; et al. Targeted disruption of the basic Kruppel-like factor gene (Klf3) reveals a role in adipogenesis. Mol. Cell. Biol. 2008, 28, 3967–3978. [Google Scholar] [CrossRef] [PubMed]
- Gubelmann, C.; Schwalie, P.C.; Raghav, S.K.; Roder, E.; Delessa, T.; Kiehlmann, E.; Waszak, S.M.; Corsinotti, A.; Udin, G.; Holcombe, W.; et al. Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network. eLife 2014, 3, e03346. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.B.; Spiegelman, B.M. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 1996, 10, 1096–1107. [Google Scholar] [CrossRef]
- Shimano, H.; Shimomura, I.; Hammer, R.E.; Herz, J.; Goldstein, J.L.; Brown, M.S.; Horton, J.D. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J. Clin. Investig. 1997, 100, 2115–2124. [Google Scholar] [CrossRef]
- Tong, Q.; Dalgin, G.; Xu, H.; Ting, C.N.; Leiden, J.M.; Hotamisligil, G.S. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science (New York, NY) 2000, 290, 134–138. [Google Scholar] [CrossRef]
- Leow, S.C.; Poschmann, J.; Too, P.G.; Yin, J.; Joseph, R.; McFarlane, C.; Dogra, S.; Shabbir, A.; Ingham, P.W.; Prabhakar, S.; et al. The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis. Development (Cambridge, England) 2016, 143, 950–961. [Google Scholar] [CrossRef]
- Wang, Y.; Sul, H.S. Pref-1 regulates mesenchymal cell commitment and differentiation through Sox9. Cell Metab. 2009, 9, 287–302. [Google Scholar] [CrossRef] [PubMed]
- Tontonoz, P.; Graves, R.A.; Budavari, A.I.; Erdjument-Bromage, H.; Lui, M.; Hu, E.; Tempst, P.; Spiegelman, B.M. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha. Nucleic Acids Res. 1994, 22, 5628–5634. [Google Scholar] [CrossRef] [PubMed]
- Hauner, H. The mode of action of thiazolidinediones. Diabetes/Metab. Res. Rev. 2002, 18 (Suppl. 2), S10–S15. [Google Scholar] [CrossRef] [PubMed]
- Lam, Y.W.F.; Duggirala, R.; Jenkinson, C.P.; Arya, R. Chapter 9—The Role of Pharmacogenomics in Diabetes. In Pharmacogenomics, 2nd ed.; Lam, Y.W.F., Scott, S.A., Eds.; Academic Press: San Diego, CA, USA, 2019; pp. 247–269. [Google Scholar]
Signalling Pathways | Effect on Adipocyte Differentiation | References |
---|---|---|
IGF-1 | Promotes | [37,38,39,40] |
Glucocorticoid | Promotes | [42,43,44,45] |
cAMP | Promotes | [46,47,48,49,50] |
TGF-β1 and 2 | Inhibits | [52,53,54,55] |
BMP2 | Promotes | [59,60] |
BMP4 | Promotes | [53,56,57,58] |
BMP7 | Promotes | [55,61,62,63,64] |
Wnt | Inhibits | [65,69,70,72] |
Hedgehog | Inhibits | [74,76] |
ERK/MAPK | Promotes | [78] |
Inhibits | [79,80] | |
P38/MAPK | Promotes | [81,82,83] |
Inhibits | [77] | |
Ras | Promotes | [37,84] |
Retinoblastoma protein | Inhibits | [85] |
Myostatin | Inhibits | [88] |
Regulator | Effect on Adipogenic Differentiation | References | |
---|---|---|---|
Chromatin Remodelling Complex | In Vitro | In Vivo | |
SWI/SNF | Promotes | - | [91] |
Lysine methyltransferases | |||
SETDB1 | Inhibits | - | [95,96] |
G9a | Inhibits | Inhibits | [98] |
Nsd2 | Promotes | Promotes | [99] |
MLL3/4 | Promotes | Inhibits | [103] |
Ezh2 | Promotes | - | [94,102] |
Ehmt1 | - | Promotes | [104] |
Lysine demethylases | |||
LSD1 | Promotes | Promotes | [95,97] |
Kdm5 | Promotes | - | [100] |
Arginine methyltransferases | |||
CARM1 | Promotes | Promotes | [90,105] |
PRMT5 | Promotes | - | [106,107] |
Histone acetyltransferases | |||
Gcn5/PCAF | Promotes | Promotes | [110] |
CBP/p300 | Promotes | Promotes | [111,112] |
Epigenetic reader BRD4 | Promotes | Promotes | [114,115] |
Histone deacetylases | |||
HDAC 1 | Inhibits | - | [117] |
HDAC 1 and 2 | Promotes | - | [119] |
HDAC 9 | Inhibits | [120] | |
Sirt 1 | Inhibits | Inhibits | [123,124,132] |
Sirt 2 | Inhibits | - | [125] |
Sirt 6 | Promotes | Promotes | [126] |
Sirt 7 | Promotes | Promotes | [121] |
DNA methyltransferase | |||
Dnmt1 | Promotes (clonal expansion) | - | [129] |
DNA demethylases | |||
Tet 1 and 2 | Promotes | - | [131] |
MicroRNAs | Target | Experimental Model | References |
---|---|---|---|
Proadipogenic | |||
MiR-143 | ERK5 (MAPK signalling pathway) | Human preadipocytes | [135] |
MiR 17-92 | RB2/P130 | 3T3-L1 cells | [138] |
MiR-125b-5p | Smad 4 | 3T3-L1 cells | [139] |
MiR 30 a and d | Runx2 | HASCs | [140] |
MiR-204 and MiR-211 | Runx2 | C3H10T1/2 | [141] |
MiR-124 | Dlx4 | 3T3-L1 cells | [136] |
MiR-210 | Tcf712 (Wnt signalling pathway) | 3T3-L1 cells | [69] |
MiR-146 | Sirt 1/FOXO1 | 3T3-L1 cells | [144] |
Antiadipogenic | |||
MiR-130 | PPARγ | 3T3-L1 cells | [142] |
MiR-27a and b | PPARγ and C/EBPα | 3T3-L1 cells | [143] |
MiR-93 | Sirt 7 and Tbx3 | miR-25-93-106b–/– mice | [145] |
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Ambele, M.A.; Dhanraj, P.; Giles, R.; Pepper, M.S. Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. Int. J. Mol. Sci. 2020, 21, 4283. https://doi.org/10.3390/ijms21124283
Ambele MA, Dhanraj P, Giles R, Pepper MS. Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. International Journal of Molecular Sciences. 2020; 21(12):4283. https://doi.org/10.3390/ijms21124283
Chicago/Turabian StyleAmbele, Melvin A., Priyanka Dhanraj, Rachel Giles, and Michael S. Pepper. 2020. "Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways" International Journal of Molecular Sciences 21, no. 12: 4283. https://doi.org/10.3390/ijms21124283
APA StyleAmbele, M. A., Dhanraj, P., Giles, R., & Pepper, M. S. (2020). Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. International Journal of Molecular Sciences, 21(12), 4283. https://doi.org/10.3390/ijms21124283