Characterising the homeostatic and hedonic markers of the susceptible phenotype

Over the years, approaches to obesity prevention and treatment have gone from focusing on genetic and other biological factors to exploring a diversity of diets and individual behavior modification interventions anchored primarily in the power of the mind, to the recent shift focusing on societal interventions to design ";temptation-proof"; physical, social, and economic environments. In spite of repeated calls to action, including those of the World Health Organization (WHO), the pandemic continues to progress. WHO recently projected that if the current lifestyle trend in young and adult populations around the world persist, by 2012 in countries like the USA, health care costs may amount to as much as 17.7% of the GDP. Most importantly, in large part due to the problems of obesity, those children may be the first generation ever to have a shorter life expectancy than that of their parents. This work presents the most current research and proposals for addressing the pandemic. Past studies have focused primarly on either genetic or behavioral causes for obesity, however today's research indicates that a strongly integrated program is the best prospect for success in overcoming obesity. Furthermore, focus on the role of society in establishing an affordable, accessible and sustainable program for implementing these lifestyle changes is vital, particularly for those in economically challenged situations, who are ultimately at the highest risk for obesity. Using studies from both neuroscience and behavioral science to present a comprehensive overview of the challenges and possible solutions, The brain-to-society approach to obesity prevention focuses on what is needed in order to sustain a healthy, pleasurable and affordable lifestyle.

Homeostatic epistemology : reliability, coherence and coordination in a Bayesian virtue epistemology

How do agents with limited cognitive capacities flourish in informationally impoverished or unexpected circumstances? Aristotle argued that human flourishing emerged from knowing about the world and our place within it. If he is right, then the virtuous processes that produce knowledge, best explain flourishing. Influenced by Aristotle, virtue epistemology defends an analysis of knowledge where beliefs are evaluated for their truth and the intellectual virtue or competences relied on in their creation. However, human flourishing may emerge from how degrees of ignorance are managed in an uncertain world. Perhaps decision-making in the shadow of knowledge best explains human wellbeing—a Bayesian approach? In this dissertation I argue that a hybrid of virtue and Bayesian epistemologies explains human flourishing—what I term homeostatic epistemology. Homeostatic epistemology supposes that an agent has a rational credence p when p is the product of reliable processes aligned with the norms of probability theory; whereas an agent knows that p when a rational credence p is the product of reliable processes such that: 1) p meets some relevant threshold for belief (such that the agent acts as though p were true and indeed p is true), 2) p coheres with a satisficing set of relevant beliefs and, 3) the relevant set of beliefs is coordinated appropriately to meet the integrated aims of the agent. Homeostatic epistemology recognizes that justificatory relationships between beliefs are constantly changing to combat uncertainties and to take advantage of predictable circumstances. Contrary to holism, justification is built up and broken down across limited sets like the anabolic and catabolic processes that maintain homeostasis in the cells, organs and systems of the body. It is the coordination of choristic sets of reliably produced beliefs that create the greatest flourishing given the limitations inherent in the situated agent.

Homeostatic regulation of free retinol-binding protein and free thyroxine pools of plasma by their plasma carrier proteins in chicken

The mechanism underlying homeostatic regulation of the plasma levels of free retinol-binding protein and free thyroxine, the systemic distribution of which is of great importance, has been investigated. A simple method has been developed to determine the rate of dissociation of a ligand from the binding protein. Analysis of the dissociation process of retinol-binding protein from prealbumin-2 reveals that the free retinol-binding protein pool undergoes massive flux, and the prealbumin-2 participates in homeostatic regulation of the free retinol-binding protein pool. Studies on the dissociation process of thyroxine from its plasma carrier proteins show that the various plasma carrier proteins share two roles. Of the two types of protein, the thyroxine-binding globulin (the high affinity binding protein) contributes only 27% of the free thyroxine in a rapid transition process, despite its being the major binding protein. But prealbumin-2, which has lower affinity towards thyroxine, participates mainly in a rapid flux of the free thyroxine pool. Thus thyroxine-binding globulin acts predominantly as a plasma reservoir of thyroxine, and also probably in the �buffering� action on plasma free thyroxine level, in the long term, while prealbumin-2 participates mainly in the maintainance of constancy of free thyroxine levels even in the short term. The existence of these two types of binding protein facilitates compensation for the metabolic flux of the free ligand and maintenance of the thyroxine pool within a very narrow range.

Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

BACKGROUND: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. METHODOLOGY/PRINCIPAL FINDINGS: Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. CONCLUSIONS/SIGNIFICANCE: During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness.

The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.

The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.

Normative life satisfaction: measurement issues and a homeostatic model

Previous studies have established that, when life satisfaction is measured over a range from 0 to 100 the mean scores of Western populations average 75 ± 2.5. The consistency of these data has given rise to the idea that life satisfaction may be held under homeostatic control. This paper further investigates this hypothesis by examining the distribution of data within populations. It also examines these data with a view to elucidating various methodological issues regarding life satisfaction measurement. In terms of the methodological issues it is concluded that measurement is best achieved using bi-directional Likert scales with at least 11 choice points. It is also determined that the life satisfaction of Western populations did not change over the decade 1980–1990, and that data derived from college students cannot be validly employed as proxy general population data. In terms of data distribution, it is calculated that the normal range of life satisfaction within Western populations lies within the range 40 to 100. The consistency of this non-normal distribution is argued to be further evidence that life satisfaction is held under homestatic control, and a descriptive model is proposed.

Caregivers as managers of subjective wellbeing: a homeostatic perspective

Background: This paper proposes that the adequacy of service delivery and caregiving to people who are disabled should be assessed using two criteria. One is the objective circumstance of living, which should be at a standard acceptable to the community at large. The other is a level of subjective wellbeing (SWB) within the normal range. Method: This latter criterion is a novel conception based on an understanding that SWB is homeostatically managed to lie normally within a narrow range of values. Results: People who have a disability are more likely than usual to have a fragile homeostatic system because of the additional life challenges imposed by their disability. Conclusions: The role of a caregiver is to provide resources and protection against strong threats to homeostasis, thereby ensuring that the person in their care has a normal-range level of SWB.

Effects of dietary fat and conjugated linoleic acid on plasma metabolite concentrations and metabolic responses to homeostatic signals in pigs

Sixteen female cross-bred (Large White × Landrace) pigs (initial weight 65 kg) with venous catheters were randomly allocated to four treatment groups in a 2×2 factorial design. The respective factors were dietary fat (25 or 100 g/kg) and dietary conjugated linoleic acid (CLA; 0 or 10 g CLA-55/kg). Pigs were fed every 3 h (close to ad libitum digestible energy intake) for 8 d and were bled frequently. Plasma glucose and non-esterified fatty acid (NEFA) responses to insulin and adrenaline challenges were determined on day 8. Plasma concentrations of NEFA were significantly increased (10·5 and 5·4 % for low- and high-fat diets respectively, P=0·015) throughout the experiment, suggesting that there was a possible increase in fat mobilisation. The increase in lipolysis, an indicator of ß-adrenergic stimulated lipolysis, was also evident in the NEFA response to adrenaline. However, the increase in plasma triacylglycerol (11·0 and 7·1 % for low- and high-fat diets respectively, P=0·008) indicated that CLA could have reduced fat accretion via decreased adipose tissue triacylglycerol synthesis from preformed fatty acids, possibly through reduced lipoprotein lipase activity. Plasma glucose, the primary substrate for de novo lipid synthesis, and plasma insulin levels were unaffected by dietary CLA suggesting that de novo lipid synthesis was largely unaffected (P=0·24 and P=0·30 respectively). In addition, the dietary CLA had no effect upon the ability of insulin to stimulate glucose removal.

Homeostatic mechanism : subjective quality of life and chronic pain

Investigates the maintenance of subjective quality of life in the presence of chronic pain. A homeostatic mechanism is proposed and examined in terms of the roles of the suggested components and how these are altered by the threat of chronic pain.

The contribution of job and partner satisfaction to the homeostatic defense of subjective wellbeing

Two studies investigate subjective wellbeing (SWB) homeostasis. The first investigates the contribution of job satisfaction (JS) and partner satisfaction (PS) to the homeostatic defense of SWB. The extant model of homeostasis does not include either variable. The second study investigates the relationship between Homeostatically Protected Mood (HPMood) and other factors involved in the homeostatic model. It has been proposed that HPMood is the basic, biologically determined, positive mood that saturates SWB and other related variables, and forms the basis of the SWB set-point. Thus, if HPMood is an individual difference and it perfuses other homeostatic variables, then HPMood should be responsible for much of the shared variance between such variables. Two comparative samples are involved. One is a group of 171 Hong Kong Chinese recruited through convenience sampling. The other is a group of 343 Australians recruited via a general population survey. Results indicate that both JS and PS predict significant variance in Global Life Satisfaction beyond the existing factors in the homeostatic model. It is also found that, after controlling for the effect of HPMood, the strength of correlations between SWB and other homeostatic variables is significantly diminished. The implications of these findings are discussed.