In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity
Abstract
:1. Introduction
2. Results
2.1. Effect of GATA3 Inhibition on Preadipocyte Proliferation, Adipogenic Capacity, Gene Expression, and Insulin Signaling
2.2. Effect of GATA3 Inhibition on Total Animal and Tissue Weight
2.3. Effect of GATA3 Inhibition on SOD and Catalase Levels in Animal Sera
2.4. Effect of GATA3 Inhibition on Gene Expression Levels from Different Adipose Tissues (Right, Left, and Omental Sites)
3. Discussion
4. Materials and Methods
4.1. In Vitro Effect of the GATA3 Inhibition
Assessment of Cell Viability and Adipogenic Capacity
4.2. In Vivo Assessment of the GATA3 Inhibition
4.2.1. Liposomes Preparation
4.2.2. Assessment of Insulin Signaling
4.2.3. Animal Care, Experimental Design and Treatment
4.2.4. Assessment of Oxidative Stress
4.2.5. Assessment of Gene Expression from Both in Vitro and in Vivo Experiments
4.3. Statistical Analysis
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- King, H.; Aubert, R.E.; Herman, W.H. Global burden of diabetes, 1995–2025: Prevalence, numerical estimates, and projections. Diabetes Care 1998, 21, 1414–1431. [Google Scholar] [CrossRef] [PubMed]
- Pi-Sunyer, X. The medical risks of obesity. Postgrad. Med. 2009, 121, 21–33. [Google Scholar] [CrossRef] [PubMed]
- Bluher, M. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes 2009, 117, 241–250. [Google Scholar] [CrossRef] [PubMed]
- Longo, M.; Zatterale, F.; Naderi, J.; Parrillo, L.; Formisano, P.; Raciti, G.A.; Beguinot, F.; Miele, C. Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int. J. Mol. Sci. 2019, 20, 2358. [Google Scholar] [CrossRef] [PubMed]
- Goossens, G.H.; Blaak, E.E.; Theunissen, R.; Duijvestijn, A.M.; Clément, K.; Tervaert, J.W.; Thewissen, M.M. Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. Mol. Immunol. 2012, 50, 142–149. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Danaei, G.; Finucane, M.M.; Lu, Y.; Singh, G.M.; Cowan, M.J.; Paciorek, C.J.; Lin, J.K.; Farzadfar, F.; Khang, Y.H.; Stevens, G.A.; et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011, 378, 31–40. [Google Scholar] [CrossRef]
- Kramer, C.K.; Zinman, B.; Retnakaran, R. Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann. Intern. Med. 2013, 159, 758–769. [Google Scholar] [CrossRef]
- Ruderman, N.; Chisholm, D.; Pi-Sunyer, X.; Schneider, S. The metabolically obese, normal-weight individual revisited. Diabetes 1998, 47, 699–713. [Google Scholar] [CrossRef]
- Bornfeldt, K.E.; Tabas, I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011, 14, 575–585. [Google Scholar] [CrossRef] [Green Version]
- Adiels, M.; Westerbacka, J.; Soro-Paavonen, A.; Häkkinen, A.M.; Vehkavaara, S.; Caslake, M.J.; Packard, C.; Olofsson, S.O.; Yki-Järvinen, H.; Taskinen, M.R.; et al. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 2007, 50, 2356–2365. [Google Scholar] [CrossRef] [PubMed]
- De Fronzo, R.A.; Ferrannini, E. Insulin Resistance: A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14, 173–194. [Google Scholar] [CrossRef]
- O’Connell, J.; Lynch, L.; Cawood, T.J.; Kwasnik, A.; Nolan, N.; Geoghegan, J.; McCormick, A.; O’Farrelly, C.; O’Shea, D. The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS ONE 2010, 5, e9997. [Google Scholar] [CrossRef]
- Karastergiou, K.; Mohamed-Ali, V. The autocrine and paracrine roles of adipokines. Mol. Cell. Endocrinol. 2010, 318, 69–78. [Google Scholar] [CrossRef] [PubMed]
- Gustafson, B.; Hammarstedt, A.; Andersson, C.X.; Smith, U. Inflamed adipose tissue: A culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 2276–2283. [Google Scholar] [CrossRef] [PubMed]
- Rosen, E.D.; MacDougald, O.A. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 2006, 7, 885–896. [Google Scholar] [CrossRef]
- Almuraikhy, S.; Kafienah, W.; Bashah, M.; Diboun, I.; Jaganjac, M.; Al-Khelaifi, F.; Abdesselem, H.; Mazloum, N.A.; Alsayrafi, M.; Mohamed-Ali, V.; et al. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance. Diabetologia 2016, 59, 2406–2416. [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 2000, 290, 134–138. [Google Scholar] [CrossRef] [PubMed]
- Tong, Q.; Tsai, J.; Tan, G.; Dalgin, G.; Hotamisligil, G.S. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol. Cell. Biol. 2005, 25, 706–715. [Google Scholar] [CrossRef]
- Batchvarova, N.; Wang, X.Z.; Ron, D. Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153). EMBO J. 1995, 14, 4654–4661. [Google Scholar] [CrossRef]
- Bezy, O.; Elabd, C.; Cochet, O.; Petersen, R.K.; Kristiansen, K.; Dani, C.; Ailhaud, G.; Amri, E.Z. Delta-interacting protein A, a new inhibitory partner of CCAAT/enhancer-binding protein beta, implicated in adipocyte differentiation. J. Biol. Chem. 2005, 280, 11432–11438. [Google Scholar] [CrossRef] [PubMed]
- Rochford, J.J.; Semple, R.K.; Laudes, M.; Boyle, K.B.; Christodoulides, C.; Mulligan, C.; Lelliott, C.J.; Schinner, S.; Hadaschik, D.; Mahadevan, M.; et al. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol. Cell. Biol. 2004, 24, 9863–9872. [Google Scholar] [CrossRef]
- Shi, X.; Shi, W.; Li, Q.; Song, B.; Wan, M.; Bai, S.; Cao, X. A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep. 2003, 4, 374–380. [Google Scholar] [CrossRef] [PubMed]
- Tong, Q.; Tsai, J.; Hotamisligil, G.S. GATA transcription factors and fat cell formation. Drug News Perspect. 2003, 16, 585–588. [Google Scholar] [CrossRef]
- Garn, H.; Renz, H. GATA-3-specific DNAzyme—A novel approach for stratified asthma therapy. Eur. J. Immunol. 2017, 47, 22–30. [Google Scholar] [CrossRef] [PubMed]
- de Souza, C.J.; Eckhardt, M.; Gagen, K.; Dong, M.; Chen, W.; Laurent, D.; Burkey, B.F. Effects of Pioglitazone on Adipose Tissue Remodeling Within the Setting of Obesity and Insulin Resistance. Diabetes 2001, 50, 1863–1871. [Google Scholar] [CrossRef] [PubMed]
- Al-Mansoori, L.; Al-Jaber, H.; Madani, A.Y.; Mazloum, N.A.; Agouni, A.; Ramanjaneya, M.; Abou-Samra, A.B.; Elrayess, M.A. Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes. Cell Signal. 2020, 75, 109735. [Google Scholar] [CrossRef]
- Dvorak, R.V.; De Nino, W.F.; Ades, P.A.; Poehlman, E.T. Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women. Diabetes 1999, 48, 2210–2214. [Google Scholar] [CrossRef]
- Al-Sulaiti, H.; Dömling, A.S.; Elrayess, M.A.M. Mediators of Impaired Adipogenesis in Obesity-Associated Insulin Resistance and T2DM. In Adipose Tissue—An Update; IntechOpen: London, UK, 2019; Chapter 7. [Google Scholar]
- Al-Jaber, H.; Al-Mansoori, L.; Elrayess, M.A. GATA-3 as a Potential Therapeutic Target for Insulin Resistance and Type 2 Diabetes Mellitus. Curr. Diabetes Rev. 2021, 17, 169–179. [Google Scholar] [CrossRef]
- Miyazaki, Y.; Mahankali, A.; Matsuda, M.; Mahankali, S.; Hardies, J.; Cusi, K.; Mandarino, L.J.; DeFronzo, R.A. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 2002, 87, 2784–2791. [Google Scholar] [CrossRef]
- Fukumura, D.; Ushiyama, A.; Duda, D.G.; Xu, L.; Tam, J.; Krishna, V.; Chatterjee, K.; Garkavtsev, I.; Jain, R.K. Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis. Circ. Res. 2003, 93, e88–e97. [Google Scholar] [CrossRef]
- Sánchez-Ceinos, J.; Guzmán-Ruiz, R.; Rangel-Zúñiga, O.A.; López-Alcalá, J.; Moreno-Caño, E.; Del Río-Moreno, M.; Romero-Cabrera, J.L.; Pérez-Martínez, P.; Maymo-Masip, E.; Vendrell, J.; et al. Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease. eLife 2021, 10, e65996. [Google Scholar] [CrossRef]
- Lefterova, M.I.; Haakonsson, A.K.; Lazar, M.A.; Mandrup, S. PPARgamma and the global map of adipogenesis and beyond. Trends Endocrinol. Metab. 2014, 25, 293–302. [Google Scholar] [CrossRef]
- Zhang, J.; Gao, Z.; Yin, J.; Quon, M.J.; Ye, J. S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-α signaling through IKK2. J. Biol. Chem. 2008, 283, 35375–35382. [Google Scholar] [CrossRef]
- Hardy, O.T.; Perugini, R.A.; Nicoloro, S.M.; Gallagher-Dorval, K.; Puri, V.; Straubhaar, J.; Czech, M.P. Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity. Surg. Obes. Relat. Dis. 2011, 7, 60–67. [Google Scholar] [CrossRef]
- Adachi, T.; Toishi, T.; Wu, H.; Kamiya, T.; Hara, H. Expression of extracellular superoxide dismutase during adipose differentiation in 3T3-L1 cells. Redox Rep. 2009, 14, 34–40. [Google Scholar] [CrossRef]
- Gustafson, B.; Gogg, S.; Hedjazifar, S.; Jenndahl, L.; Hammarstedt, A.; Smith, U. Inflammation and impaired adipogenesis in hypertrophic obesity in man. Am. J. Physiol. Endocrinol. Metab. 2009, 297, E999–E1003. [Google Scholar] [CrossRef]
- Panee, J. Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes. Cytokine 2012, 60, 1–12. [Google Scholar] [CrossRef]
- Sartipy, P.; Loskutoff, D.J. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc. Natl. Acad. Sci. USA 2003, 100, 7265–7270. [Google Scholar] [CrossRef]
- Al-Sulaiti, H.; Diboun, I.; Banu, S.; Al-Emadi, M.; Amani, P.; Harvey, T.M.; Dömling, A.S.; Latiff, A.; Elrayess, M.A. Triglyceride profiling in adipose tissues from obese insulin sensitive, insulin resistant and type 2 diabetes mellitus individuals. J. Transl. Med. 2018, 16, 175. [Google Scholar] [CrossRef] [Green Version]
- Najlah, M.; Jain, M.; Wan, K.-W.; Ahmed, W.; Albed Alhnan, M.; Phoenix, D.A.; Taylor, K.M.; Elhissi, A. Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells. J. Liposome Res. 2018, 28, 74–85. [Google Scholar] [CrossRef]
- Gayoso-Diz, P.; Otero-González, A.; Rodriguez-Alvarez, M.X.; Gude, F.; García, F.; De Francisco, A.; Quintela, A.G. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: Effect of gender and age: EPIRCE cross-sectional study. BMC Endocr. Disord. 2013, 13, 47. [Google Scholar] [CrossRef]
- Misra, A.; Gopalan, H.; Jayawardena, R.; Hills, A.P.; Soares, M.; Reza-Albarrán, A.A.; Ramaiya, K.L. Diabetes in developing countries. J. Diabetes 2019, 11, 522–539. [Google Scholar] [CrossRef] [PubMed]
- Elrayess, M.A.; Almuraikhy, S.; Kafienah, W.; Al-Menhali, A.; Al-Khelaifi, F.; Bashah, M.; Zarkovic, K.; Zarkovic, N.; Waeg, G.; Alsayrafi, M.; et al. 4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance. Free Radic. Biol. Med. 2017, 104, 129–137. [Google Scholar] [CrossRef] [PubMed]
- Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25, 402–408. [Google Scholar] [CrossRef] [PubMed]
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Al-Jaber, H.; Mohamed, N.A.; Govindharajan, V.K.; Taha, S.; John, J.; Halim, S.; Alser, M.; Al-Muraikhy, S.; Anwardeen, N.R.; Agouni, A.; et al. In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity. Int. J. Mol. Sci. 2022, 23, 11142. https://doi.org/10.3390/ijms231911142
Al-Jaber H, Mohamed NA, Govindharajan VK, Taha S, John J, Halim S, Alser M, Al-Muraikhy S, Anwardeen NR, Agouni A, et al. In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity. International Journal of Molecular Sciences. 2022; 23(19):11142. https://doi.org/10.3390/ijms231911142
Chicago/Turabian StyleAl-Jaber, Hend, Nura A. Mohamed, Vijay K. Govindharajan, Samir Taha, Jomon John, Sharique Halim, Maha Alser, Shamma Al-Muraikhy, Najeha Rizwana Anwardeen, Abdelali Agouni, and et al. 2022. "In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity" International Journal of Molecular Sciences 23, no. 19: 11142. https://doi.org/10.3390/ijms231911142
APA StyleAl-Jaber, H., Mohamed, N. A., Govindharajan, V. K., Taha, S., John, J., Halim, S., Alser, M., Al-Muraikhy, S., Anwardeen, N. R., Agouni, A., Elhissi, A., Al-Naemi, H. A., Al-Mansoori, L., & Elrayess, M. A. (2022). In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity. International Journal of Molecular Sciences, 23(19), 11142. https://doi.org/10.3390/ijms231911142