Hédi Soula | INSA Lyon (original) (raw)
Papers by Hédi Soula
La cirsimarine, un nouveau flavonoïde d’origine végétale inhibe la lipogenèse et diminue l’accrétion adipeuse chez la souris
ABSTRACT Un flavonoïde glycosylé d’origine végétale, la cirsimarine, a montré en laboratoire une ... more ABSTRACT Un flavonoïde glycosylé d’origine végétale, la cirsimarine, a montré en laboratoire une forte activité lipolytique sur adipocytes isolées. Afin de tester le potentiel pharmacologique de cette molécule in vivo, des souris mâle CD-1 ont reçu quotidiennement pendant 18 jours une injection intrapéritonale de cirsimarine (25 ou 50 mg/kg) ou de son véhicule. Au sacrifice, les différents dépôts de tissus adipeux sont disséqués et pesés et la cellularité (i.e. taille et nombre de cellules) du tissu adipeux épididymal est analysée. Les souris traitées à la cirsimarine (25 ou 50 mg/kg.j) présentent une réduction significative de l’adiposité avec une diminution de la masse des tissus adipeux blancs épididymal (-25 and -28%, P<0.005) et rétropéritonéal (-29% and -37%, P<0.005) comparée aux souris contrôles. Cette diminution de la masse adipeuse est due à une diminution du diamètre moyen des adipocytes (-5% et -8% pour 25 and 50 mg/kg.j, P<0.05) résultant en une diminution de 14% et 35% (P<0.005) du volume adipocytaire moyen sans variation du nombre d’adipocytes par dépôt adipeux. L’administration chronique de cirsimarine (25 ou 50 mg/kg.j) diminue de 18 et 27% la lipogenèse adipocytaire avérée par la mesure de l’incorporation de 14C-acétate. Sur adipocytes isolés, la cirsimarine exerce une forte activité anti-lipogénique avec une IC50 de l’ordre du micromolaire (1.28 ± 0.04 µM). Nos résultats suggèrent donc que la cirsimarine limite l’accrétion adipeuse chez la souris en exerçant un puissant effet anti-lipogènique sur le tissu adipeux blanc.
The Effect of Membrane Receptor Clustering on Spatio-temporal Cell Signalling Dynamics
Lecture Notes in Computer Science, 2012
A mathematical model of leptin resistance
Mathematical Biosciences, 2015
Obesity is often associated with leptin resistance, which leads to a physiological system with hi... more Obesity is often associated with leptin resistance, which leads to a physiological system with high leptin concentration but unable to respond to leptin signals and to regulate food intake. We propose a mathematical model of the leptin-leptin receptors system, based on the assumption that leptin is a regulator of its own receptor activity, and investigate its qualitative behavior. Based on current knowledge and previous models developed for body weight dynamics in rodents, the model includes the dynamics of leptin, leptin receptors and the regulation of food intake and body weight. It displays two stable equilibria, one representing a healthy state and the other one an obese and leptin resistant state. We show that a constant leptin injection can lead to leptin resistance and that a temporal variation in some parameter values influencing food intake can induce a change of equilibrium and a pathway to leptin resistance and obesity.
Techniques et sciences informatiques, 2007
Nous présentons ici une démarche émergentiste de la modélisation cellulaire, basée sur une simula... more Nous présentons ici une démarche émergentiste de la modélisation cellulaire, basée sur une simulation multi-agents. Nous décrivons l'ensemble du processus de création du modèle, depuis le projet scientifique jusqu'aux méthodes d'implémentation, en insistant particulièrement sur le modèle d'interactions entre agents qui est la base de notre simulation. Enfin, des résultats préliminaires montrant l'émergence de structures organisées sont présentés pour illustrer l'intérêt de l'approche proposée. ABSTRACT. Systems biology and cell simulation started together and maintain a controvertible relationship within the scope of global approaches and emergence-driven approaches. Here, we present a multi-agent based model for cell simulation. We describe the whole model creation process, from its scientific project perspective to implementation considerations. The agents interactions model will be particularly detailed. Finally, preliminary results showing self-organised structures will be presented to demonstrate the interest of this approach.
Functional space approach for evolutionary algorithms
Chemico-biological interactions
Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydrox... more Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydroxy-2-nonenal (HNE) and 4-hydroxy-2-hexenal (HHE) are produced in several oxidative stress associated diseases from peroxidation of n-6 and n-3 polyunsaturated fatty acids, respectively. Both are able to form covalent adducts with many biomolecules. Particularly, proteins adduction can induce structural and conformational changes and impair biological function, which may be involved in the toxicity of hydroxy-alkenals. The aim of this study was to compare the effect of 4-hydroxy-2-alkenals to several chemically related derivatives in order to clarify the physico-chemical requirement of their toxicity. L6 muscle cells were treated with HHE, HNE and parent derivatives (acetal derivative, trans-alkenals and alkanals). Viability and necrosis were estimated using MTT, LDH and caspase-3 tests. LogLC50 (Lethal Concentration 50) was then tested for correlation with adducts formation (estimated usi...
Stochastic Chemical Reactions Methods
Impact of Receptor clustering on the membrane-based stage of a signalling pathway
Recurrent spiking neural networks can provide biologically inspired model of robot controller. We... more Recurrent spiking neural networks can provide biologically inspired model of robot controller. We study here the dynamics of large size randomly connected networks thanks to "mean field theory". Mean field theory allows to compute their dynamics under the assumption that the dynamics of individual neuronsare stochastically independent. We restrict ourselves to the simple case of homogeneous centered gaussian independent synaptic weights. First a theoretical study allows to derive the mean-field dynamics using a large deviation approach. This dynamics is characterized in function of an order parameter which is the normalized variance of the coupling. Then various applications are reviewed which show the applicative potentiality of the approach.
Comments to the Editor. Reply to the Comment by VP Shkilev on" Anomalous versus slowed-down Brownian diffusion in the ligand-binding equilibrium
PLoS ONE, 2014
Dynamics of body weight and food intake can be studied by temporally perturbing food availability... more Dynamics of body weight and food intake can be studied by temporally perturbing food availability. This perturbation can be obtained by modifying the amount of available food over time while keeping the overall food quantity constant. To describe food intake dynamics, we developed a mathematical model that describes body weight, fat mass, fat-free mass, energy expenditure and food intake dynamics in rats. In addition, the model considers regulation of food intake by leptin, ghrelin and glucose. We tested our model on rats experiencing temporally variable food availability. Our model is able to predict body weight and food intake variations by taking into account energy expenditure dynamics based on a memory of the previous food intake. This model allowed us to estimate this memory lag to approximately 8 days. It also explains how important variations in food availability during periods longer than these 8 days can induce body weight gains.
PLoS ONE, 2014
Introduction: Adipocyte size and body fat distribution are strongly linked to the metabolic compl... more Introduction: Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods: Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results: The initial body weight of the rats was 46565.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion: Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.
A Neural Model for Animats Brain
Artificial Neural Nets and Genetic Algorithms, 2001
ABSTRACT A model of a neural controller – NeuroReactive controller – is proposed. This model exhi... more ABSTRACT A model of a neural controller – NeuroReactive controller – is proposed. This model exhibits the learning abilities of artificial neural networks and the modular structure of reactive control, based on asynchronous spikes propagation. Some applications are given as well.
Reply to the Comment by V. P. Shkilev on "Anomalous versus Slowed-Down Brownian Diffusion in the Ligand-Binding Equilibrium
Biophysical journal, 2014
Cirsimarin, a potent antilipogenic flavonoid, decreases fat deposition in mice intra-abdominal adipose tissue
International Journal of Obesity, 2010
We previously reported that the flavonoid cirsimarin exerts in vitro a strong lipolytic activity ... more We previously reported that the flavonoid cirsimarin exerts in vitro a strong lipolytic activity on isolated adipocytes. This study was therefore designed to evaluate in vivo the effects of cirsimarin on white adipose tissue (WAT) accretion in mice. Male CD1 mice were injected daily with either vehicle (intraperitoneal (i.p.)) or cirsimarin (25 or 50 mg kg(-1) per day, i.p.) for 18 days. Mice were killed and fat pads weighted. Epididymal fat pads were used for cellularity measurement. Effects of cirsimarin treatment on lipolysis and lipogenesis in WAT were assessed. Mice treated with 25 or 50 mg kg(-1) per day cirsimarin showed a decrease in retroperitoneal (-29 and -37% respectively, P<0.005) and epididymal (-25 and -28% respectively, P<0.005) fat pad weights compared with controls. This effect was restricted to intra-abdominal WAT as no difference was noticed for subcutaneous inguinal WAT. The decrease in intra-abdominal WAT accretion was due to a decrease in adipose cell diameter (-5 and -8% for 25 and 50 mg kg(-1) per day cirsimarin, respectively) resulting in a 14 and 35% decrease in adipose cell volume while no change was noticed in total adipocyte number. Direct injection of cirsimarin (50 mg kg(-1)) to rats did not trigger lipolysis. In contrast, cirsimarin showed in vivo as well as in vitro a strong antilipogenic activity, which may be the critical aspect of its effects on fat accretion in mice. The inhibitory concentration 50% of cirsimarin on lipogenic activity in isolated adipocytes was found to be 1.28±0.04 μM. Cirsimarin given orally reduced intra-abdominal fat accretion in mice. Cirsimarin exerts potent antilipogenic effect and decreases adipose tissue deposition in mice. Cirsimarin could therefore be a potential candidate for the treatment of obesity.
Evolving spiking neurons nets to control an animat
Artificial Neural Nets and Genetic Algorithms, 2003
The RBF-Gene Model
Artificial Neural Nets and Genetic Algorithms, 2003
BMC Biophysics, 2012
Background: In the classical view, cell membrane proteins undergo isotropic random motion, that i... more Background: In the classical view, cell membrane proteins undergo isotropic random motion, that is a 2D Brownian diffusion that should result in an homogeneous distribution of concentration. It is, however, far from the reality: Membrane proteins can assemble into so-called microdomains (sometimes called lipid rafts) which also display a specific lipid composition. We propose a simple mechanism that is able to explain the colocalization of protein and lipid rafts. Results: Using very simple mathematical models and particle simulations, we show that a variation of membrane viscosity directly leads to variation of the local concentration of diffusive particles. Since specific lipid phases in the membrane can account for diffusion variation, we show that, in such a situation, the freely diffusing proteins (or any other component) still undergo a Brownian motion but concentrate in areas of lower diffusion. The amount of this so-called overconcentration at equilibrium issimply related to the ratio of diffusion coefficients between zones of high and low diffusion. Expanding the model to include particle interaction, we show that inhomogeneous diffusion can impact particles clusterization as well. The clusters of particles were more numerous and appear for a lower value of interaction strength in the zones of low diffusion compared to zones of high diffusion. Conclusion: Provided we assume stable viscosity heterogeneity in the membrane, our model propose a simple mechanism to explain particle concentration heterogeneity. It has also a non-trivial impact on density of particles when interaction is added. This could potentially have an impact on membrane chemical reactions and oligomerization.
Frontiers in Physiology, 2014
Experimental measurements of the mobility of macromolecules, especially proteins, in cells and th... more Experimental measurements of the mobility of macromolecules, especially proteins, in cells and their membranes consistently report transient subdiffusion with possibly position-dependent-non-homogeneous-properties. However, the spatiotemporal dynamics of protein mobility when transient subdiffusion is restricted to a subregion of space is still unclear. Here, we investigated the spatial distribution at equilibrium of proteins undergoing transient subdiffusion due to continuous-time random walks (CTRW) in a restricted subregion of a two-dimensional space. Our Monte-Carlo simulations suggest that this process leads to a non-homogeneous spatial distribution of the proteins at equilibrium, where proteins increasingly accumulate in the CTRW subregion as its anomalous properties are increasingly marked. In the case of transient CTRW, we show that this accumulation is dictated by the asymptotic Brownian regime and not by the initial anomalous transient dynamics. Moreover, our results also show that this dominance of the asymptotic Brownian regime cannot be simply generalized to other scenarios of transient subdiffusion. In particular, non-homogeneous transient subdiffusion due to hindrance by randomly-located immobile obstacles does not lead to such a strong local accumulation. These results suggest that, even though they exhibit the same time-dependence of the mean-squared displacement, the different scenarios proposed to account for subdiffusion in the cell lead to different protein distribution in space, even at equilibrium and without coupling with reaction.
Model of adipose tissue cellularity dynamics during food restriction
Journal of Theoretical Biology, 2015
Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases relat... more Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution.
La cirsimarine, un nouveau flavonoïde d’origine végétale inhibe la lipogenèse et diminue l’accrétion adipeuse chez la souris
ABSTRACT Un flavonoïde glycosylé d’origine végétale, la cirsimarine, a montré en laboratoire une ... more ABSTRACT Un flavonoïde glycosylé d’origine végétale, la cirsimarine, a montré en laboratoire une forte activité lipolytique sur adipocytes isolées. Afin de tester le potentiel pharmacologique de cette molécule in vivo, des souris mâle CD-1 ont reçu quotidiennement pendant 18 jours une injection intrapéritonale de cirsimarine (25 ou 50 mg/kg) ou de son véhicule. Au sacrifice, les différents dépôts de tissus adipeux sont disséqués et pesés et la cellularité (i.e. taille et nombre de cellules) du tissu adipeux épididymal est analysée. Les souris traitées à la cirsimarine (25 ou 50 mg/kg.j) présentent une réduction significative de l’adiposité avec une diminution de la masse des tissus adipeux blancs épididymal (-25 and -28%, P<0.005) et rétropéritonéal (-29% and -37%, P<0.005) comparée aux souris contrôles. Cette diminution de la masse adipeuse est due à une diminution du diamètre moyen des adipocytes (-5% et -8% pour 25 and 50 mg/kg.j, P<0.05) résultant en une diminution de 14% et 35% (P<0.005) du volume adipocytaire moyen sans variation du nombre d’adipocytes par dépôt adipeux. L’administration chronique de cirsimarine (25 ou 50 mg/kg.j) diminue de 18 et 27% la lipogenèse adipocytaire avérée par la mesure de l’incorporation de 14C-acétate. Sur adipocytes isolés, la cirsimarine exerce une forte activité anti-lipogénique avec une IC50 de l’ordre du micromolaire (1.28 ± 0.04 µM). Nos résultats suggèrent donc que la cirsimarine limite l’accrétion adipeuse chez la souris en exerçant un puissant effet anti-lipogènique sur le tissu adipeux blanc.
The Effect of Membrane Receptor Clustering on Spatio-temporal Cell Signalling Dynamics
Lecture Notes in Computer Science, 2012
A mathematical model of leptin resistance
Mathematical Biosciences, 2015
Obesity is often associated with leptin resistance, which leads to a physiological system with hi... more Obesity is often associated with leptin resistance, which leads to a physiological system with high leptin concentration but unable to respond to leptin signals and to regulate food intake. We propose a mathematical model of the leptin-leptin receptors system, based on the assumption that leptin is a regulator of its own receptor activity, and investigate its qualitative behavior. Based on current knowledge and previous models developed for body weight dynamics in rodents, the model includes the dynamics of leptin, leptin receptors and the regulation of food intake and body weight. It displays two stable equilibria, one representing a healthy state and the other one an obese and leptin resistant state. We show that a constant leptin injection can lead to leptin resistance and that a temporal variation in some parameter values influencing food intake can induce a change of equilibrium and a pathway to leptin resistance and obesity.
Techniques et sciences informatiques, 2007
Nous présentons ici une démarche émergentiste de la modélisation cellulaire, basée sur une simula... more Nous présentons ici une démarche émergentiste de la modélisation cellulaire, basée sur une simulation multi-agents. Nous décrivons l'ensemble du processus de création du modèle, depuis le projet scientifique jusqu'aux méthodes d'implémentation, en insistant particulièrement sur le modèle d'interactions entre agents qui est la base de notre simulation. Enfin, des résultats préliminaires montrant l'émergence de structures organisées sont présentés pour illustrer l'intérêt de l'approche proposée. ABSTRACT. Systems biology and cell simulation started together and maintain a controvertible relationship within the scope of global approaches and emergence-driven approaches. Here, we present a multi-agent based model for cell simulation. We describe the whole model creation process, from its scientific project perspective to implementation considerations. The agents interactions model will be particularly detailed. Finally, preliminary results showing self-organised structures will be presented to demonstrate the interest of this approach.
Functional space approach for evolutionary algorithms
Chemico-biological interactions
Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydrox... more Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydroxy-2-nonenal (HNE) and 4-hydroxy-2-hexenal (HHE) are produced in several oxidative stress associated diseases from peroxidation of n-6 and n-3 polyunsaturated fatty acids, respectively. Both are able to form covalent adducts with many biomolecules. Particularly, proteins adduction can induce structural and conformational changes and impair biological function, which may be involved in the toxicity of hydroxy-alkenals. The aim of this study was to compare the effect of 4-hydroxy-2-alkenals to several chemically related derivatives in order to clarify the physico-chemical requirement of their toxicity. L6 muscle cells were treated with HHE, HNE and parent derivatives (acetal derivative, trans-alkenals and alkanals). Viability and necrosis were estimated using MTT, LDH and caspase-3 tests. LogLC50 (Lethal Concentration 50) was then tested for correlation with adducts formation (estimated usi...
Stochastic Chemical Reactions Methods
Impact of Receptor clustering on the membrane-based stage of a signalling pathway
Recurrent spiking neural networks can provide biologically inspired model of robot controller. We... more Recurrent spiking neural networks can provide biologically inspired model of robot controller. We study here the dynamics of large size randomly connected networks thanks to "mean field theory". Mean field theory allows to compute their dynamics under the assumption that the dynamics of individual neuronsare stochastically independent. We restrict ourselves to the simple case of homogeneous centered gaussian independent synaptic weights. First a theoretical study allows to derive the mean-field dynamics using a large deviation approach. This dynamics is characterized in function of an order parameter which is the normalized variance of the coupling. Then various applications are reviewed which show the applicative potentiality of the approach.
Comments to the Editor. Reply to the Comment by VP Shkilev on" Anomalous versus slowed-down Brownian diffusion in the ligand-binding equilibrium
PLoS ONE, 2014
Dynamics of body weight and food intake can be studied by temporally perturbing food availability... more Dynamics of body weight and food intake can be studied by temporally perturbing food availability. This perturbation can be obtained by modifying the amount of available food over time while keeping the overall food quantity constant. To describe food intake dynamics, we developed a mathematical model that describes body weight, fat mass, fat-free mass, energy expenditure and food intake dynamics in rats. In addition, the model considers regulation of food intake by leptin, ghrelin and glucose. We tested our model on rats experiencing temporally variable food availability. Our model is able to predict body weight and food intake variations by taking into account energy expenditure dynamics based on a memory of the previous food intake. This model allowed us to estimate this memory lag to approximately 8 days. It also explains how important variations in food availability during periods longer than these 8 days can induce body weight gains.
PLoS ONE, 2014
Introduction: Adipocyte size and body fat distribution are strongly linked to the metabolic compl... more Introduction: Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods: Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results: The initial body weight of the rats was 46565.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion: Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.
A Neural Model for Animats Brain
Artificial Neural Nets and Genetic Algorithms, 2001
ABSTRACT A model of a neural controller – NeuroReactive controller – is proposed. This model exhi... more ABSTRACT A model of a neural controller – NeuroReactive controller – is proposed. This model exhibits the learning abilities of artificial neural networks and the modular structure of reactive control, based on asynchronous spikes propagation. Some applications are given as well.
Reply to the Comment by V. P. Shkilev on "Anomalous versus Slowed-Down Brownian Diffusion in the Ligand-Binding Equilibrium
Biophysical journal, 2014
Cirsimarin, a potent antilipogenic flavonoid, decreases fat deposition in mice intra-abdominal adipose tissue
International Journal of Obesity, 2010
We previously reported that the flavonoid cirsimarin exerts in vitro a strong lipolytic activity ... more We previously reported that the flavonoid cirsimarin exerts in vitro a strong lipolytic activity on isolated adipocytes. This study was therefore designed to evaluate in vivo the effects of cirsimarin on white adipose tissue (WAT) accretion in mice. Male CD1 mice were injected daily with either vehicle (intraperitoneal (i.p.)) or cirsimarin (25 or 50 mg kg(-1) per day, i.p.) for 18 days. Mice were killed and fat pads weighted. Epididymal fat pads were used for cellularity measurement. Effects of cirsimarin treatment on lipolysis and lipogenesis in WAT were assessed. Mice treated with 25 or 50 mg kg(-1) per day cirsimarin showed a decrease in retroperitoneal (-29 and -37% respectively, P<0.005) and epididymal (-25 and -28% respectively, P<0.005) fat pad weights compared with controls. This effect was restricted to intra-abdominal WAT as no difference was noticed for subcutaneous inguinal WAT. The decrease in intra-abdominal WAT accretion was due to a decrease in adipose cell diameter (-5 and -8% for 25 and 50 mg kg(-1) per day cirsimarin, respectively) resulting in a 14 and 35% decrease in adipose cell volume while no change was noticed in total adipocyte number. Direct injection of cirsimarin (50 mg kg(-1)) to rats did not trigger lipolysis. In contrast, cirsimarin showed in vivo as well as in vitro a strong antilipogenic activity, which may be the critical aspect of its effects on fat accretion in mice. The inhibitory concentration 50% of cirsimarin on lipogenic activity in isolated adipocytes was found to be 1.28±0.04 μM. Cirsimarin given orally reduced intra-abdominal fat accretion in mice. Cirsimarin exerts potent antilipogenic effect and decreases adipose tissue deposition in mice. Cirsimarin could therefore be a potential candidate for the treatment of obesity.
Evolving spiking neurons nets to control an animat
Artificial Neural Nets and Genetic Algorithms, 2003
The RBF-Gene Model
Artificial Neural Nets and Genetic Algorithms, 2003
BMC Biophysics, 2012
Background: In the classical view, cell membrane proteins undergo isotropic random motion, that i... more Background: In the classical view, cell membrane proteins undergo isotropic random motion, that is a 2D Brownian diffusion that should result in an homogeneous distribution of concentration. It is, however, far from the reality: Membrane proteins can assemble into so-called microdomains (sometimes called lipid rafts) which also display a specific lipid composition. We propose a simple mechanism that is able to explain the colocalization of protein and lipid rafts. Results: Using very simple mathematical models and particle simulations, we show that a variation of membrane viscosity directly leads to variation of the local concentration of diffusive particles. Since specific lipid phases in the membrane can account for diffusion variation, we show that, in such a situation, the freely diffusing proteins (or any other component) still undergo a Brownian motion but concentrate in areas of lower diffusion. The amount of this so-called overconcentration at equilibrium issimply related to the ratio of diffusion coefficients between zones of high and low diffusion. Expanding the model to include particle interaction, we show that inhomogeneous diffusion can impact particles clusterization as well. The clusters of particles were more numerous and appear for a lower value of interaction strength in the zones of low diffusion compared to zones of high diffusion. Conclusion: Provided we assume stable viscosity heterogeneity in the membrane, our model propose a simple mechanism to explain particle concentration heterogeneity. It has also a non-trivial impact on density of particles when interaction is added. This could potentially have an impact on membrane chemical reactions and oligomerization.
Frontiers in Physiology, 2014
Experimental measurements of the mobility of macromolecules, especially proteins, in cells and th... more Experimental measurements of the mobility of macromolecules, especially proteins, in cells and their membranes consistently report transient subdiffusion with possibly position-dependent-non-homogeneous-properties. However, the spatiotemporal dynamics of protein mobility when transient subdiffusion is restricted to a subregion of space is still unclear. Here, we investigated the spatial distribution at equilibrium of proteins undergoing transient subdiffusion due to continuous-time random walks (CTRW) in a restricted subregion of a two-dimensional space. Our Monte-Carlo simulations suggest that this process leads to a non-homogeneous spatial distribution of the proteins at equilibrium, where proteins increasingly accumulate in the CTRW subregion as its anomalous properties are increasingly marked. In the case of transient CTRW, we show that this accumulation is dictated by the asymptotic Brownian regime and not by the initial anomalous transient dynamics. Moreover, our results also show that this dominance of the asymptotic Brownian regime cannot be simply generalized to other scenarios of transient subdiffusion. In particular, non-homogeneous transient subdiffusion due to hindrance by randomly-located immobile obstacles does not lead to such a strong local accumulation. These results suggest that, even though they exhibit the same time-dependence of the mean-squared displacement, the different scenarios proposed to account for subdiffusion in the cell lead to different protein distribution in space, even at equilibrium and without coupling with reaction.
Model of adipose tissue cellularity dynamics during food restriction
Journal of Theoretical Biology, 2015
Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases relat... more Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution.