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 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human population has slowly transformed from the "hunter-gatherer" period to the current environment of high energy consumption, minimal physical activity and a lifestyle that includes stress and anxiety. Modeling the current environment in the laboratory can help to elucidate mechanisms responsible for the development of obesity, diabetes and, ultimately, the metabolic syndrome. Using the visible burrow system (VBS) model of social stress we have begun to examine the short- and long-term consequences of chronic social stress on energy homeostasis. We demonstrated that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity and have additionally determined that this occurs, in part, through changes in food intake amount and behavior. Changes in body weight and body composition are similar or greater when animals are maintained on a high fat diet. These data suggest that consumption of a high-fat diet during social stress in the VBS, while it does not appear to affect development of a social hierarchy, enhances the effect that chronic stress has on body composition and may be more representative of what happens in humans in modern society where the typical diet has progressively moved toward higher calorie, high-fat foods.
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PMID:Chronic social stress in a changing dietary environment. 1684 4

The human body, when under threat, elicits a set of neuroendocrine responses, including an increased secretion of glucocorticoids (GCs) and catecholamines from the adrenal gland and the activation of the sympathetic nervous system. These hormonal secretions allow a "fight or flight" response by mobilizing endogenous substrate and inducing a state of insulin resistance in the liver and skeletal muscles. Although the stress response was essential in ancient times to survive physical aggression, this threat has disappeared in our industrialized societies. However, in today's environment, the same stress responses can be elicited by emotional stimuli or professional and social stress. Such psychological stress may be protracted and unrelated to an increased metabolic demand. Thus, the energy mobilized is not used but is stored in visceral fat depots by the combined action of hypercortisolism and hyperinsulinemia. In addition, chronic activation of the stress system causes suppression of the gonadal, growth hormone (GH), and thyroid axes. These metabolic disturbances, in concert, lead to the clinical expression of a number of comorbidities including central obesity, hypertension, dyslipidemia, and endothelial dysfunction, all components of the metabolic syndrome and cardiometabolic risk factors. Moreover, chronic stress has deleterious effects on the brain and, in particular, affects hippocampal structure and function leading to cognitive and mood disturbances. Importantly, this stress-induced clinical phenotype is likely to be exaggerated in the presence of physical inactivity, resulting in a "stress-induced/exercise deficient" phenotype. Assuming that the stress response is a neuroendocrine mechanism that occurs in anticipation of physical action, then physical activity should be the natural means to prevent the consequences of stress. Indeed, accumulating evidence documents the beneficial effects of regular exercise in preventing or ameliorating the metabolic and psychological comorbidities induced by chronic stress. These benefits are thought to derive from a central effect of exercise to reduce the sensitivity to stress and also peripheral actions influencing metabolic functions and, in particular, insulin sensitivity and the partitioning of fuels toward oxidation rather than storage. It is concluded that chronic psychosocial stress, in the presence of physical inactivity, is likely to contribute to the epidemic of cardiometabolic and emotional disease of our current society. The way to prevent and combat this burden is by regular exercise.
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PMID:The protective role of exercise on stress system dysregulation and comorbidities. 1714 41

Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. Although there are strong associations between the incidence of obesity with stress and elevated levels of hormones such as cortisol, there are limited animal models to allow investigation of the etiology of increased adiposity resulting from exposure to stress. Perhaps more importantly, an animal model that mirrors the consequences of stress in humans will provide a vehicle to develop rational clinical therapy to treat or prevent adverse outcomes from exposure to chronic social stress. In the visible burrow system (VBS) model of chronic social stress mixed gender colonies are housed for 2 week periods during which male rats of the colony quickly develop a dominance hierarchy. We found that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity that occurs, in part, through neuroendocrine alterations and changes in food intake amount. Although subordinate rats are hyperphagic following social stress they do not increase their intake of sucrose solution as control and dominants do suggesting that they are anhedonic. Consumption of a high fat diet does not appear to affect development of a social hierarchy and appears to enhance the effect that chronic stress has on body composition. The visible burrow system (VBS) model of social stress may be a potential laboratory model for studying stress-associated metabolic disease, including the metabolic syndrome.
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PMID:Dynamic body weight and body composition changes in response to subordination stress. 1751 62

Obesity, lipid disorders, type 2 diabetes, high blood pressure and coronary heart disease are frequently encountered in wealthy populations. All these disorders frequently occur as clusters, constituting the metabolic syndrome. It is currently admitted that insulin resistance plays a central role in the pathogenesis of this syndrome. Stress responses include activation of the sympathetic nervous system and stimulation of epinephrine and cortisol release. These hormones may over the long term reduce insulin sensitivity. Cortisol may also favour the development of central obesity. In healthy individuals, mental stress increases heart rate, but simultaneously decreases vascular resistance in skeletal muscle. This results in a moderate increase in blood pressure, and an acute increase in insulin-mediated glucose disposal. In obese patients, mental stress elicits responses which differ widely from those of healthy individuals. While mental stress enhances catecholamine-mediated energy expenditure in obese patients to the same extent as in lean subjects, it fails to decrease systemic vascular resistance due to endothelial dysfunction. This leads to enhanced blood pressure responses and the absence of stimulation of glucose disposal in obese subjects during mental stress. It can be hypothesized that repeated professional or social stress may activate the sympathoadrenal system, resulting in high cortisol levels, stimulation of the sympathetic nervous system, and epinephrine secretion. All these factors may eventually lead to the development of central obesity and insulin resistance. Furthermore, the blood pressure responses to mental stress may be enhanced in insulin-resistant individuals, favouring the development of vascular complications.
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PMID:Stress and metabolism. 1837 Jul 4

Obesity and visceral fat accumulation are key features of the metabolic syndrome that represents one of the main health problems in western societies due to its neurovascular and cardiovascular complications. Epidemiological studies have identified chronic stress exposure as an important risk factor for the development of obesity and metabolic syndrome, but also psychiatric diseases, especially affective disorders. However, it is still unclear if chronic stress has merely transient or potentially lasting effects on body composition. Here, we investigated the effects of chronic social stress during the adolescent period on body fat composition in mice one year after the cessation of the stressor. We found that stress exposure during the adolescent period decreases subcutaneous fat content, without change in visceral fat, and consequently increases the visceral fat/subcutaneous fat ratio in adulthood. Further, we demonstrated that treatment with a selective serotonin reuptake inhibitor (paroxetine) during stress exposure prevented later effects on body fat distribution. These results from a recently validated chronic stress paradigm in mice provide evidence that stressful experiences during adolescence can alter body fat distribution in adulthood, thereby possibly contributing to an increased risk for metabolic diseases. Antidepressant treatment disrupted this effect underlining the link between the stress hormone system, metabolic homeostasis and affective disorders.
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PMID:Chronic social stress during adolescence in mice alters fat distribution in late life: prevention by antidepressant treatment. 1895 Dec 48

Over the last decades the burden of disease in Western countries has shifted from comparably easily treated infectious diseases to more complex diseases, such as the metabolic syndrome, cardiovascular disease, and psychiatric disorders. A common characteristic of these illnesses is the interplay of multiple genetic and nongenetic factors, which eventually results in the manifestation of disease symptoms. Large-scale epidemiological studies in humans have resulted in the identification of various environmental and genetic risk factors, which contribute to the onset, duration, and severity of disease. While tremendous progress has been made, it is still impossible to predict which combination of risk factors will result in the manifestation of a specific illness. This lack of knowledge is also frequently reflected in inadequate treatment strategies, which mainly focus on symptom reversal rather than targeting the cause of the diseases. One of the most prominent environmental risk factors described for numerous diseases is chronic exposure to stressful situations. In this paper we address clinical and preclinical evidence of chronic stress as a risk factor for disease and introduce a novel, high-throughput mouse model for chronic social stress. We can show that this model has a high degree of construct, face, and predictive validity in terms of physiological, behavioral, and gene expression changes. We further illustrate how novel animal models of chronic social stress can help to unravel the complex interaction of individual genetic vulnerability and environmental risk factors.
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PMID:Chronic stress and individual vulnerability. 1912 Jan 7

Abdominal obesity is prevalent and often accompanied by an array of metabolic perturbations including elevated blood pressure, dyslipidemia, impaired glucose tolerance or insulin resistance, a prothrombotic state, and a proinflammatory state, together referred to as the metabolic syndrome. The metabolic syndrome greatly increases coronary heart disease (CHD) risk. Social stress also increases CHD although the mechanisms through which this occurs are not completely understood. Chronic stress may result in sustained glucocorticoid production, which is thought to promote visceral obesity. Thus, one hypothesis is that social stress may cause visceral fat deposition and the metabolic syndrome, which, in turn increases CHD. CHD is caused by coronary artery atherosclerosis (CAA) and its sequelae. Cynomolgus monkeys (Macaca fascicularis) are a well-established models of CAA. Social subordination may be stressful to cynomolgus monkeys and result in hypercortisolemia and exacerbated CAA in females. Herein is reviewed a body of literature which suggests that social stress increases visceral fat deposition in cynomolgus monkeys, that subordinate females are more likely than dominants to have visceral obesity, that females with visceral obesity have behavioral and physiological characteristics consistent with a stressed state, and that females with high ratios of visceral to subcutaneous abdominal fat develop more CAA. While these relationships have been most extensively studied in cynomolgus macaques, obesity-related metabolic disturbances are also observed in other primate species. Taken together, these observations support the view that the current obesity epidemic is the result of a primate adaptation involving the coevolution with encephalization of elaborate physiological systems to protect against starvation and defend stored body fat in order to feed a large and metabolically demanding brain. Social stress may be engaging these same physiological systems, increasing the visceral deposition of fat and its sequelae, which increase CHD risk.
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PMID:Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation. 1945 15

Several psychiatric disorders increase the risk of cardiovascular disease, including posttraumatic stress disorder and major depression. While the precise mechanism for this association has not yet been established, it has been shown that certain disorders promote an unfavorable lipid profile. To study the interaction of stress and lipid dysregulation, we utilized chronic social defeat stress (CSDS), a mouse model of chronic stress with features of posttraumatic stress disorder and major depression. Following exposure to CSDS, mice were given access to either regular chow or a Western-style diet high in fat and cholesterol (HFD). The combination of social stress and HFD resulted in significant perturbations in lipid regulation, including two key features of the metabolic syndrome: increased plasma levels of non-HDL cholesterol and intrahepatic accumulation of triglycerides. These effects were accompanied by a number of changes in the expression of hepatic genes involved in lipid regulation. Transcriptional activity of LXR, SREBP1c, and ChREBP were significantly affected by exposure to HFD and CSDS. We present CSDS as a model of social stress induced lipid dysregulation and propose that social stress alters lipid metabolism by increasing transcriptional activity of genes involved in lipid synthesis.
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PMID:Chronic social defeat stress disrupts regulation of lipid synthesis. 2012 12

Socioeconomic stress associated with financial and psychosocial stress is widespread in society. A comprehensive body of research indicates that low socioeconomic status and social stress is associated with a broad spectrum of health risks. This paper reviews epidemiological evidence demonstrating the association between chronic social stress and development of obesity and symptoms leading to metabolic syndrome. The cumulative effects of socioeconomic stress on health and well being are evident throughout the lifespan, affecting children, adolescents, and adults. While the links between stress and metabolic disease are documented, the mechanisms remain less well understood. Animal models are well established and have provided opportunities to systematically investigate contributing mechanisms that may be targeted to develop treatment and prevention strategies against metabolic disorders arising from exposure to chronic social stress.
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PMID:Metabolic syndrome: links to social stress and socioeconomic status. 2188 60

Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome. Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors. Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice. In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys(3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm. Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not. In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide. Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen. In contrast, old GHSR KO mice did not show these alterations after chronic social defeat. These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.
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PMID:Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress. 2334 Nov 96


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