“…Each nullcline represents the steady state of one variable when holding the other variable fixed. This decomposes the feedback loop into two arms 40 , 41 : one arm in which A induces R , and the other arm in which R inhibits A . The crossing points of the two nullcline curves are the fixed points of the system.…”
“…Each nullcline represents the steady state of one variable when holding the other variable fixed. This decomposes the feedback loop into two arms 40 , 41 : one arm in which A induces R , and the other arm in which R inhibits A . The crossing points of the two nullcline curves are the fixed points of the system.…”
“…The DIP model suggests that there is no set-point but rather there are two intervention points (IPs) between which there is an unregulated zone, or zone of indifference. The lower intervention point (LIP) defines a weight below which active physiological feedback mechanisms kick The Hall-Guo model [125] and (b) the operating point model [132]. In the Hall-Guo model expenditure or intake is plotted as a function of body weight.…”
Section: (D) the Dual Intervention Point Modelmentioning
confidence: 99%
“…Figure 3Two different models for regulation of body weight. ( a ) The Hall–Guo model [125] and ( b ) the operating point model [132]. In the Hall–Guo model expenditure or intake is plotted as a function of body weight.…”
Section: Reconciling the Set-point And Dynamic Equilibrium Modelsmentioning
confidence: 99%
“…Bar et al [132] presented a model that is very similar to the Hall–Guo model [125] that they called the ‘operating point’ model specifically to distinguish it from the set-point idea (figure 3 b ). The model is designed primarily to explain animal studies where rodents are under and over fed in a controlled way, and then their reaction is reported after these levels of intervention.…”
Section: Reconciling the Set-point And Dynamic Equilibrium Modelsmentioning
Body weight and fatness appear to be regulated phenomena. Several different theoretical models are available to capture the essence of this idea. These include the set-point, dynamic equilibrium, adiposity force, control theory-settling point, Hall–Guo, operation point and dual intervention point (DIP) models. The set-point model posits a single reference point around which levels of fat are regulated. The dynamic equilibrium model suggests that the apparent regulation of body fat around a reference point is an illusion owing to the necessary impacts of weight change on energy expenditure. Control theory focuses on the importance of feedback gain and suggests set-point and dynamic equilibrium are ends of a continuum of feedback gain. Control theory models have also been called ‘settling point’ models. The Hall–Guo, operation point and DIP models also bring together the set-point and dynamic equilibrium ideas into a single framework. The DIP proposes a zone of indifference where dynamic equilibrium ‘regulation’ predominates, bounded by upper and lower intervention points beyond which physiological mechanisms are activated. The drifty gene hypothesis is an idea explaining where this individual variation in the upper intervention point might come from. We conclude that further experiments to test between the models are sorely required.
This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
“…This aspect may be especially relevant to understand how to improve and rescue the therapeutic ability of living cells upon scenarios of, for example, relapsing inflammation, which occur in several inflammatory chronic diseases. [ 6,7 ] The therapeutic action of MSCs has been ascribed to several cellular components, with the secretome—which includes soluble and insoluble (e.g., extracellular vesicles) factors released to the extracellular space—being the most studied component of MSCs action. [ 8 ]…”
The stimulation of mesenchymal stromal cells (MSCs) with inflammatory molecules is often employed to boost their therapeutic effect. Prolonged exposure to inflammatory molecules has been explored to improve their action since MSCs therapies seem to be improved transiently with such stimuli. However, the possibility of cyclically stimulating MSCs to recover their optimized therapeutic potential is still to be elucidated, although the efficacy of cell‐based therapies may be dependent on the ability to readapt to the relapse pathological conditions. Here, we report the response of MSCs, encapsulated in alginate hydrogels and cultured for 22 days, using three different regimes: single, continuous, and intermittent stimulation with IFNγ. Exposure to IFNγ led to a decrease in the secretion of IL‐10, which was cyclically countered by IFNγ weaning. Conditioned media collected at different stages of pulsatile stimulation showed an immunomodulatory potential towards macrophages, which directly correlated with IL‐10 concentration in media. To understand whether the correlation between cyclic stimulation of MSCs and other biological actions could be observed, the effect on endothelial cells was studied, showcasing an overall modest influence on tube formation. Overall, our results describe the response of encapsulated MSCs to unusual pulsatile simulation regimens, exploring encapsulated MSCs as a living on‐demand release systems of tailored secretomes with recoverable immunomodulatory action.This article is protected by copyright. All rights reserved
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