Revista Eletrônica Gestão & Saúde ISSN: 1982-4785 Pires JG Artigo de Discussão Some insights into an integrative mathematical model: a prototype- model for bodyweight and energy homeostasis Algumas discussões em um modelo matemático integrativo: um modelo protótipo para homeostase do peso corporal e energia Algunos debates sobre un modelo matemático integrador: un modelo prototipo para la homeostasis del peso corporal y energía Jorge Guerra Pires1 functions and roles seem fuzzy, most hormones seem to be piloting the same Abstract: The ambition of this undertaking. The key challenge from a document is to set in evidence the mathematical modeling perspective is prerequisite for integrative how to separate properly the (mathematical) models, mechanism- mechanisms of each hormone. The kind based models, for appetite/bodyweight of pursuit presented herein could initiate control. For achieving this goal, it is an imperative cascade of mathematical provided a scrutinized literature review modeling applied to metabolism of and it is organized them in such a way bodyweight control and energy to make the point. The quantitative homeostasis. methods exploited by the authors are Descriptors: Insulin; Glucose; called differential equations solved Homeostasis; Mathematical Models; numerically; they are discussed briefly Systems Biology. since it is not our goal herein to handle details. On the current state of the art, Resumo: O escopo deste trabalho é there is no mathematical model to the colocar em evidência a necessidade de best of the author’s knowledge targeting modelos matemáticos integrativos, at integrating several hormones at once modelos baseados em mecanismos, para in mathematical descriptions: even for investigar controle de apetite e peso single hormones, the literature is either corporal. De forma a atingir essa meta, occasional or do not exist at all; it is uma revisão seletiva da literatura é depicted some results for simple models apresentada e o material é organizado already built. As it can be seen, the de modo a defender a visão. Os métodos quantitativos empregados são chamados 1 Department of Information Engineering, Computer Science and Mathematics (University of L'Aquila)/ Institute equações diferenciais resolvidas of Systems Analysis and Computer Science (IASI- CNR)/CAPES Foundation (Ministry of Education of Brazil). numericamente; estas não são discutidas E-mail: [email protected] Rev. Gest.Saúde (Brasília) Vol.07, n. 03, Set Ano 2016 p. 1271-88 1271 Revista Eletrônica Gestão & Saúde ISSN: 1982-4785 Pires JG Some insights into a integrative... em detalhes devido ao fato de fugir do presenta y el material se organiza para desígnio do trabalho. No estado correte defender la visión. Los métodos da arte, aparentemente não existem cuantitativos utilizados son llamados modelos que buscam descrever ecuaciones diferenciales resuelven matematicamente hormônios de uma numéricamente; éstos no se discuten en forma única e integrada, mesmo para detalle debido al hecho de escapar del hormônios únicos, a literatura ou é alcance del trabajo. En el estado actual insuficiente ou não existe em muitos de la técnica correte, al parecer, non hay casos. Resultados preliminares são modelos que tratan de describir apresentados para algumas tentativas matemáticamente las hormonas de incipientes. Como pode ser visto, a manera única e integrada, incluso para funcionalidade e importância de cada las hormonas individuales, la literatura hormônio pode ser abstrusa, em muitas es escasa o inexistente. Los resultados casos poder-se-ia chegar à conclusão de preliminares se presentan en algunos que vários hormônios empenham a intentos incipientes. Como puede verse, mesma função. O desafio-chave do la funcionalidad y la importancia de ponto de vista matemático é como cada hormona pueden ser confusos, en entender a posição de cada hormônio no muchos casos se puede llegar a la processo como um todo. Trabalhos conclusión de que varias hormonas como o defendido aqui podem gerar cometen la misma función. El desafío uma onda de modelos matemáticos clave de un punto de vista matemático aplicados ao controle de peso e es cómo entender la posición de cada homeostase energético. hormona en el proceso como un todo. Descritores: Insulina; Glucose; Proyectos como abogado por aquí Homeostase; Modelos Matemáticos; puede generar una ola de modelos Biologia de Sistemas. matemáticos aplicados para el control de peso y la homeostasis energética. Resumen: El objetivo de este trabajo es Descriptores. Insulina; Glucosa; poner de relieve la necesidad de Homeostasis; Modelos Matemáticos; modelos matemáticos de integración, Biología de Sistemas. basado en modelos mecanismos para controlar el apetito y el peso corporal. 1. Introduction Con el fin de lograr este objetivo, una The determination to unify for revision selectivo de la literatura se integrating in the biological sciences is Rev. Gest.Saúde (Brasília) Vol.07, n. 03, Set Ano 2016 p. 1271-88 1272 Revista Eletrônica Gestão & Saúde ISSN: 1982-4785 Pires JG Some insights into a integrative... ubiquitous in several areas these days, and co-works(4), it was also detected an eminent photograph of this key independently by Tam and co-works(5). attempt is Systems Biology, in theories comparable to multiscale modeling; e.g. 1.1 Objective(s) /motivations from gene to metabolism, from The objective of this work is to set in metabolism to cell behavior, from cell evidence the prerequisite for integrative behavior to tissue, and similar modeling mathematical models, mechanism-based paradigms. By taking advantage of the models, for appetite/bodyweight possibilities brought alongside systems control. This ambition was born from biology and alike, one can bump into the surveillance that no existent model audacious philosophies and paradigms; so far to the best of our knowledge had e.g. the virtual human(1), or virtual integrated efficaciously more than one pancreas(2). hormone, even for one hormone the Physiologically speaking, glucose models are infrequent or centered in one control, which implies in energy hormone, i.e. insulin; see(4) for a nice homeostasis and bodyweight changes, is case. Notwithstanding we provide a a quite dense and intricate bio-process. literature survey and some mathematical Accordingly, it is a process with players discussions, it is out of our scope to in different hierarchal phases and either discuss mathematical details or stages. As one illustration of such an make a complete literature review. As allegation, one could pick out “eating” sub-objectives, we can point out: a) (food intake) that is controlled by discuss some problems in the medical ghrelin and fat mass controlled by literature when reporting hormone leptin. On this paper, the researchers workings, that is, try to point out where dissert on an idealized insight called needs further investigations; b) pave the unceremoniously the “big glucose way for an upcoming (ongoing) model; model." In view of that, the perception c) captivate the reader regarding was born from the perceived lack of mathematical models in hormonal models that mathematically take a control. The motivation for pursuing glimpse of glucose control in an this goal(s) is that metabolic medical integrative line of attack, typically it is conditions related to eating is quite done using predominantly insulin(3); a common in our modern society, and seminar study is presented by Jacquier solutions rarely can be tested a priori, e.g. diets or medical products. Rev. Gest.Saúde (Brasília) Vol.07, n. 03, Set Ano 2016 p. 1271-88 1273 Revista Eletrônica Gestão & Saúde ISSN: 1982-4785 Pires JG Some insights into a integrative... result of this system failing to work 1.2 Organization of the manuscript properly or completely is diabetes and In the upcoming section, section 2, it is leptin resistance(7). Accordingly, discussed some literatures. In the metabolism is the imperative bio- following section, section 3, it is process in which living systems balance discussed briefly the methods. Since the energy available and the energy this work is not an “experimental” demanded on such a way that the work, this section is added for the sake organism will not find itself in of completeness. The authors plan to circumstances of lacking energy after a come back in other papers with more profusion of foodstuff(8-9); medical details since it is an ongoing project. conditions comparable to anorexia The next section, section 4, it is nervosa and morbid obesity are in provided some results and discussions, general positively correlated with it was overlapped in a single section due malfunctioning of the metabolic to the nature of the current work, which machinery. Independently of scientific is not presenting a set of experiments advances, our body works, and it is a and make the interpretation, rather it is miracle of control system in practice. to present an idea, the aim on this Accordingly, glucose is constantly section is to give the reader a flavor of converted to glycogen, "the battery of the current endeavors. Finally, section living systems," and it is constantly 5, presents the conclusions and final brought back to the bloodstream in remarks. Some references, scrutinized, times of necessity. As puts it(9), “This are given for the reader to have an idea [energy deposit mechanism] ensures an of the pillars of the current work. adequate plasma concentration of energy substrates to sustain tissue 2. Literature review metabolism at all times.” 2.1 The “big glucose model”: an Notwithstanding the astonishing integrative interpretation of glucose- advancements made over the past few bodyweight control decades in unscrambling many of the The overlapping of hormonal molecular pathways involved in energy receptiveness to nutrient (load) (homeostasis) regulation, a rather availability is primary for metabolic cloudy understanding of “how all the control(0); likely the best examples of pieces fit together to function as an medical conditions that appear as a integrated system”(5) is what can be Rev. Gest.Saúde (Brasília) Vol.07, n. 03, Set Ano 2016 p. 1271-88 1274 Revista Eletrônica Gestão & Saúde ISSN: 1982-4785 Pires JG Some insights into a integrative..