(2015) 14:48793. Using prebiotic or probiotic drugs modifies the microbiota and changes the diet and pharmacological treatments of obesity (13, 91). Endocrinology. Also, it varies from whole-body to cellular regeneration. Although there are some differences, the related molecular mechanisms and components of the thyroid axis in zebrafish is comparable to mammals. doi: 10.1007/s10561-019-09773-8, 7. Goel A, Gupta M, Aggarwal R. Gut microbiota and liver disease. (2010) 16:1210. doi: 10.1038/nm.2224, 46. Cancers. doi: 10.1002/hec.3833. Therefore, in order to trigger regeneration activity in human tissues, an exogenous stimulus is needed. Since many kidney diseases are caused by mono/polygenic mutations, zebrafish is used to both reveal the underlying genetic mutation and pathophysiology and model for drug screening in the hopes of personalized medicine) (7173). Curr Opin Pharmacol. Intraperitoneal injection of streptozotocin (STZ), a common way of chemical-induced diabetes in rodents, can effectively ablate cells, although higher concentration is needed (9, 93). (2016) 238:25766. In this concept, through recent decades, cell therapy, and regenerative medicine hold a great promise in representing novel therapies for several types of diseases. 
This process, similar to previous ones, involves many signaling pathways like Notch signaling which is known as an inhibitory pathway in the retina and motor neuron regeneration. Stoletov K, Fang L, Choi SH, Hartvigsen K, Hansen LF, Hall C, et al. Bae HC, Park HJ, Wang SY, Yang HR, Lee MC, Han H-S. Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem cells. (2007) 104:1131621. Obesity researchers can also use zebrafish as a qualified animal model since adipose tissue development is based on the same principals in both species, studies also suggest similar genetic factors (83). Nutritional approach, along with genetic alteration were used to generate models, for instance, immersing zebrafish in glucose solution or over feeding it with a commercial food. However, in the matter of regeneration studies, scientists need a model with something more than mentioned characteristics, a model that possesses regeneration capacity. cell zebrafish gastrulation basis coordinated spreading tissue physical Salmi TM, Tan VWT, Cox AG. In this respect, generating an appropriate animal model to investigate the unknown mechanisms and experimenting with drug and other therapeutic interventions is necessary. Behrouzi A, Nafari AH, Siadat SD. Therefore, a novel therapy to restore pancreatic function without the need for exogenous insulin seems an ideal escape route. 
Ellis C, Ramzy A, Kieffer TJ. Schlegel A. Due to limitations in repeating blood sampling, metabolism assays like hormone testing and insulin tolerance tests are all much harder to conduct on zebrafish (50). 
Biomaterials. Taken together, it can be concluded that unique features of zebrafish like high regenerative capacity, easier disease induction, low-cost housing, high maturation rate, and fecundity along with the utility of zebrafish in modeling endocrine and metabolic disorders, make it a better choice for developing personalized regenerative treatment. However, more recent researches have been demonstrated that animal models with the ability of tissue regeneration are more suitable choices for regenerative medicine studies in endocrine disorders, typically diabetes mellitus. Arjmand B, Goodarzi P, Mohamadi-Jahani F, Falahzadeh K, Larijani B. Personalized regenerative medicine. Endocrinol. Nature. Notably, choosing a suitable animal model is considered as a pivotal step in a preclinical study. The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Dis Models Mech. Pringle ES, Wertman J, Melong N, Coombs AJ, Young AL, O'Leary D, et al. 
(2009) 312:1423. For example, difficulty in the evaluation of engraftment in the early steps, the adverse effects of irradiation regimes, prolonged engraftment assessing procedures, special maintenance requirements for immunosuppressed animals, and restriction in the number of animals that can be screened which consequently raise the overall cost and duration. The most common registered trials in the field of regenerative medicine are focused on cardiovascular diseases, nervous system diseases and musculoskeletal conditions (34). doi: 10.1242/dmm.036004, 95. There are different genetic approaches, one is NTR/MTZ ablation system in which transgenic zebrafish with cell expression of the bacterial NTR enzyme are exposed to the metronidazole (MTZ) which is the substrate of the enzyme and converts in to a cytotoxic compound inducing cell apoptosis. Recent investigations have been implemented in zebrafish in endocrine-related disorders using omics technologies. Another surprising area in zebrafish is neural regeneration. Mageed M, Berner D, Jlke H, Hohaus C, Brehm W, Gerlach K. Is sheep lumbar spine a suitable alternative model for human spinal researches? doi: 10.1053/j.ackd.2017.10.011, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. Up to now, several species of animals have been modeled to identify the mechanism of multiple diseases. Dev Biol. (2019) 12:dmm036004. Any animal model to study human diseases has some limitations which in this case are: Fundamental differences of systems like reproductive and respiratory systems between zebrafish and humans. Morphometrical comparison study. FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. 
How to make insulin-producing pancreatic cells for diabetes treatment. Clin J Am Soc Nephrol. Zebrafish are 23 cm in length which makes whole organ analysis or transplantation much easier. Nat Med. Since these organs and their interplay are quite similar in zebrafish, it has been used to model obesity (9, 62). (2018) 2:122. Therefore, a global effort has been devoted to diabetes mellitus investigations. zebrafish parkinson Zebrafish model for human long QT syndrome. Cell therapy and regenerative medicine are the major causes of remarkable revolution in different fields of medicine in recent decades. zebrafish cinj doi: 10.1007/s00018-012-1037-y, 86. Moreover, it was found that long-term exposure to environmental chemicals has caused physiological alterations and various disorders, some of which seem to be associated with changes in the endocrine system. Herzog W, Sonntag C, von der Hardt S, Roehl HH, Varga ZM, Hammerschmidt M. Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. BA contributed substantially to the conception and design of the study. (2017) 1007:17997. MP conducted search strategy and data collection. Zebrafish and mammals seem to be similar in glucose dynamic throughout embryonic development and Pck1 regulation (79). Alloxan is another chemical which can kill cells in both adult zebrafish and its larvae (9). Proc Natl Acad Sci USA. (1992) 4:24758. (2020) 240:124970. doi: 10.1016/j.chemosphere.2019.124970, 112. 
Generally, in order to achieve the most efficient treatment, an understanding of the underlying pathophysiology and drug efficacy, animal model is crucial. Studying NAFLD in zebrafish has many advantages (85, 86): 1 The possibility of visualizing the liver by staining the lipids, 2 The feasibility of liver dissection in order to conduct analysis. This fascinating feature is due to its high regenerative capability and amenability to various genetic approaches. The cell proliferation increases sharply after tissue damage based on various underlying processes, for instance, different genes are expressed in the endocardium. Monsarrat P, Vergnes J-N, Planat-Bnard V, Ravaud P, Kmoun P, Senseb L, et al. Vascular lipid accumulation, lipoprotein oxidation, and macrophage lipid uptake in hypercholesterolemic zebrafish. The zebrafish as a model of vascular development and disease. doi: 10.1016/j.biomaterials.2010.08.097, 21. Molinari E, Sayer JA. doi: 10.1210/en.2008-0816, 32. McCarthy F, Kingdom J, Kenny L, Walsh S. Animal models of preeclampsia; uses and limitations. Another mutation in cytochrome p450 family2 subfamily R member1 (cyp2r1) gene which makes the deficiency of 1,25(OH)2D3 (the active form of vitamin D), increases adiposity and causes growth retardation (9). Folia Histochem Cytobiol. Simoni E, Orsini G, Chicca M, Bettini S, Franceschini V, Martini A, et al. In addition, mutant lines like Foie gras [essential for endoplasmic reticulum (ER) to Golgi vascular transport] and cdipthi599Tg/+ (cytidine diphosphate-diacylglycerol-inositol 3-phosphatidyltransferase which causes lipid accumulation in hepatocytes) often cause fatty liver at larval stages, mostly because of ER stress. Since there are serious prohibitions in performing tests and researches on human, as alternatives, animal models providing the possibility of various investigations to discover the mechanism of different diseases (46). Gerontology. (2011) 32:56578. Accordingly, some of the studied models of zebrafish DM, obesity, and NAFLD as symbols of metabolic and endocrine-related disorders are discussed. Michel M, Page-McCaw PS, Chen W, Cone RD. (2017) 19:90915. 
Stem cell and obesity: current state and future perspective. Furthermore, studying molecular signals of regeneration revealed adenosine signaling role in -cells proliferation (88). doi: 10.1016/S0012-1606(03)00436-6, 97. Cell Regenerat. Moreover, since zebrafish can be utilized for high-throughput non-biased chemical screening, there is a growing rate in its employing for in vivo drug discovery researches (112). In addition, zebrafish is a suitable model for studying a variety of different situations. In this review, we discuss the features of zebrafish that make it a desirable animal model, the advantages of zebrafish and recent research that shows zebrafish is a promising animal model for personalized regenerative diseases. Although its size is an advantage in many procedures it can mean inadequate sample for a number of analysis. Cells. (2016) 5:82635. seq atac zebrafish cell endothelial enhancers assisted developmentally identification robust active fans using Freund PA. Introduction to the Issue Ethical Aspects of Experimentation With Human Subjects. Modelling pancreatic -cell inflammation in zebrafish identifies the natural product wedelolactone for human islet protection. Personalized regenerative medicine lays the ground for developing effective therapies for these conditions. EBioMedicine. Their importance and priority are determined according to their level of similarity to human physio-anatomical characteristics. 
Sumi S, Gu Y, Hiura A, Inoue K. Stem cells and regenerative medicine for diabetes mellitus. Stem cells applications in regenerative medicine and disease therapeutics. Human gut microbiota is known to be unique and diverse which has an important role in developing diseases, inflammation, and different clinical outcomes (89, 90). Exclusive human factors affecting metabolism such as lifestyle, behavioral, and socioeconomic factors cannot be replicated in zebrafish. Therefore, Figure 1 shows some of different approaches experimented to model the metabolic diseases which were mentioned in the text, and some other endocrine disorders. Weger BD, Weger M, Grling B, Schink A, Gobet C, Keime C, et al. Stem cells: a revolution in therapeuticsrecent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Einstein O, Friedman-Levi Y, Grigoriadis N, Ben-Hur T. Transplanted neural precursors enhance host brain-derived myelin regeneration. (2019) 20:1739. doi: 10.3390/ijms20071739, 78. 
Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Accordingly, scientists have been introduced some alternatives to ease different processes in animal studies. Misregulation of these pathways can cause cancerous tissue in humans (66). Eighty-two percent of proteins that code human genes are found to have close relations with zebrafish genes that most of them are thought to be associated with human diseases. doi: 10.1016/j.placenta.2011.03.010, 47. Obesity is the result of positive energy balance, when the energy intake is more than its expenditure it involves regulation among different organs such as brain, liver and adipose tissue. Cell Mol Life Sci. Inducing insulin resistance and liver inflammation may be involved in the development of NAFLD and changes in gut bacterial composition lead to obesity. Detection of biomarkers to differentiate endocrine disruption from hepatotoxicity in zebrafish (Danio rerio) using proteomics.
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