SciCombinator

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Concept: Homeostasis

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BACKGROUND: Despite the increasing understanding of the mechanisms relating to weight loss and maintenance, there are currently no validated public health interventions that are able to achieve sustained long-term weight loss or to stem the increasing prevalence of obesity in the population. We aimed to examine the models of energy balance underpinning current research about weight-loss intervention from the field of public health, and to determine whether they are consistent with the model provided by basic science. EMBASE was searched for papers published in 2011 on weight-loss interventions. We extracted details of the population, nature of the intervention, and key findings for 27 articles. DISCUSSION: Most public health interventions identified were based on a simple model of energy balance, and thus attempted to reduce caloric consumption and/or increase physical activity in order to create a negative energy balance. There appeared to be little consideration of homeostatic feedback mechanisms and their effect on weight-loss success. It seems that there has been a lack of translation between recent advances in understanding of the basic science behind weight loss, and the concepts underpinning the increasingly urgent efforts to reduce excess weight in the population. SUMMARY: Public health weight-loss interventions seem to be based on an outdated understanding of the science. Their continued failure to achieve any meaningful, long-term results reflects the need to develop intervention science that is integrated with knowledge from basic science. Instead of asking why people persist in eating too much and exercising too little, the key questions of obesity research should address those factors (environmental, behavioral or otherwise) that lead to dysregulation of the homeostatic mechanism of energy regulation. There is a need for a multidisciplinary approach in the design of future weight-loss interventions in order to improve long-term weight-loss success.

Concepts: Health, Cancer, Nutrition, Obesity, Physical exercise, Weight loss, Dieting, Homeostasis

177

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.

Concepts: Nutrition, Obesity, Adipose tissue, Cybernetics, Feedback, Negative feedback, Dieting, Homeostasis

87

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimize performance is to heat acclimatize. Heat acclimatization should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in an euhydrated state and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vests), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimizing the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events for hydration and body cooling opportunities when competitions are held in the heat.

Concepts: Competition, Olympic Games, Homeostasis, Acclimatization, FIFA World Cup, FIFA, FIFA World Rankings, 2014 Winter Olympics

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In this study, we hypothesized that dynamics of sleep time obtained over consecutive days of extended sleep in a laboratory reflect an individual’s optimal sleep duration (OSD) and that the difference between OSD and habitual sleep duration (HSD) at home represents potential sleep debt (PSD). We found that OSD varies among individuals and PSD showed stronger correlation with subjective/objective sleepiness than actual sleep time, interacting with individual’s vulnerability of sleep loss. Furthermore, only 1 h of PSD takes four days to recover to their optimal level. Recovery from PSD was also associated with the improvement in glycometabolism, thyrotropic activity and hypothalamic-pituitary-adrenocortical axis. Additionally, the increase (rebound) in total sleep time from HSD at the first extended sleep would be a simple indicator of PSD. These findings confirmed self-evaluating the degree of sleep debt at home as a useful clinical marker. To establish appropriate sleep habits, it is necessary to evaluate OSD, vulnerability to sleep loss, and sleep homeostasis characteristics on an individual basis.

Concepts: Sleep, Sleep deprivation, Individual, Homeostasis, Recovery model, Degree of a polynomial, Recovery, Unihemispheric slow-wave sleep

41

Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using fluorescent reporters for AMPK activity, Akt activity, and cytosolic NADH/NAD+ redox. Across various conditions, including glycolytic or mitochondrial inhibition or cell proliferation, we observed distinct patterns of AMPK activity, including both stable adaptation and highly dynamic behaviors such as periodic oscillations and irregular fluctuations that indicate a failure to reach a steady state. Fluctuations in AMPK activity, Akt activity, and cytosolic NADH/NAD+ redox state were temporally linked in individual cells adapting to metabolic perturbations. By monitoring single-cell dynamics in each of these contexts, we identified PI3K/Akt regulation of glycolysis as a multifaceted modulator of single-cell metabolic dynamics that is required to maintain metabolic stability in proliferating cells.

Concepts: Bacteria, Metabolism, Adenosine triphosphate, Mitochondrion, Cytosol, Cellular respiration, Systems theory, Homeostasis

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Spexin is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in children.

Concepts: Obesity, Novel, Homeostasis, Childhood obesity, Adult

31

The assumption that small changes in hydration status are readily compensated by homeostatic mechanisms has been little studied. In this study, the influence of hypohydration on cognition was examined.

Concepts: Homeostasis, Assumption of Mary

31

The brain regulates energy homeostasis in the organism. Under resource shortage, the brain takes priority over peripheral organs for energy supply. But can the brain also down-regulate its own consumption to favor survival? We show that the brain of Drosophila specifically disables the costly formation of aversive long-term memory (LTM) upon starvation, a physiological state required for appetitive LTM formation. At the neural circuit level, the slow oscillations normally triggered in two pairs of dopaminergic neurons to enable aversive LTM formation were abolished in starved flies. Transient artificial activation of these neurons during training restored LTM formation in starved flies but at the price of a reduced survival. LTM formation is thus subject to adaptive plasticity that helps survival under food shortage.

Concepts: Nervous system, Psychology, Neuron, Brain, Human brain, Hippocampus, Dopamine, Homeostasis

30

Living organisms have unique homeostatic abilities, maintaining tight control of their local environment through interconversions of chemical and mechanical energy and self-regulating feedback loops organized hierarchically across many length scales. In contrast, most synthetic materials are incapable of continuous self-monitoring and self-regulating behaviour owing to their limited single-directional chemomechanical or mechanochemical modes. Applying the concept of homeostasis to the design of autonomous materials would have substantial impacts in areas ranging from medical implants that help stabilize bodily functions to ‘smart’ materials that regulate energy usage. Here we present a versatile strategy for creating self-regulating, self-powered, homeostatic materials capable of precisely tailored chemo-mechano-chemical feedback loops on the nano- or microscale. We design a bilayer system with hydrogel-supported, catalyst-bearing microstructures, which are separated from a reactant-containing ‘nutrient’ layer. Reconfiguration of the gel in response to a stimulus induces the reversible actuation of the microstructures into and out of the nutrient layer, and serves as a highly precise ‘on/off’ switch for chemical reactions. We apply this design to trigger organic, inorganic and biochemical reactions that undergo reversible, repeatable cycles synchronized with the motion of the microstructures and the driving external chemical stimulus. By exploiting a continuous feedback loop between various exothermic catalytic reactions in the nutrient layer and the mechanical action of the temperature-responsive gel, we then create exemplary autonomous, self-sustained homeostatic systems that maintain a user-defined parameter–temperature–in a narrow range. The experimental results are validated using computational modelling that qualitatively captures the essential features of the self-regulating behaviour and provides additional criteria for the optimization of the homeostatic function, subsequently confirmed experimentally. This design is highly customizable owing to the broad choice of chemistries, tunable mechanics and its physical simplicity, and may lead to a variety of applications in autonomous systems with chemo-mechano-chemical transduction at their core.

Concepts: Organism, Chemical reaction, Chemistry, Control theory, Cybernetics, Feedback, Negative feedback, Homeostasis

28

Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis.

Concepts: Nervous system, Developmental biology, Systems theory, Mouse, Mice, Microglia, Homeostasis, A Lifetime