Endocrinology of the stress response Charmandari, Evangelia; Tsigos, Constantine; Chrousos, George
Annual review of physiology,
01/2005, Letnik:
67, Številka:
1
Journal Article
Recenzirano
The stress response is subserved by the stress system, which is located both in the central nervous system and the periphery. The principal effectors of the stress system include ...corticotropin-releasing hormone (CRH); arginine vasopressin; the proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, the glucocorticoids; and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks, and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development and may account for a number of endocrine, metabolic, autoimmune, and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors, and the timing of the stressful events, given that prenatal life, infancy, childhood, and adolescence are critical periods characterized by increased vulnerability to stressors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting ...not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient's obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.
: Stress is a state of threatened homeostasis or disharmony caused by intrinsic or extrinsic adverse forces and is counteracted by an intricate repertoire of physiologic and behavioral responses ...that aim to reestablish the challenged body equilibrium. The adaptive stress response depends upon an elaborate neuroendocrine, cellular, and molecular infrastructure, the stress system. Crucial functions of the stress system response are mediated by the hypothalamic‐pituitary‐adrenal (HPA) axis and the central and peripheral components of the autonomic nervous system (ANS). The integrity of the HPA axis and the ANS and their precise interactions with other CNS components are essential for a successful response to the various stressors. Chronic stress represents a prolonged threat to homeostasis by persistent or frequently repeated stressors and may lead to manifestations that characterize a wide range of diseases and syndromes. Such states progressively lead to a deleterious overload with complications caused by both the persistent stressor and the detrimental prolongation of the adaptive response. The metabolic syndrome can be described as a state of deranged metabolic homeostasis characterized by the combination of central obesity, insulin resistance, dyslipidemia, and hypertension. The incidence of both obesity and the metabolic syndrome in modern Western societies has taken epidemic proportions over the past decades and often correlates with indices of stress in the affected populations. Stress, primarily through hyperactivation of the HPA axis, appears to contribute to the accumulation of fat tissue, and vice versa, obesity itself seems to constitute a chronic stressful state and may cause HPA axis dysfunction. In addition, the description of obesity as a systemic low grade inflammatory condition that contributes to the derangement of the metabolic equilibrium implies that the proinflammatory cytokines which are secreted by the adipocytes hold a potentially important pathogenetic role. In this article we describe the physiology of the stress system response, with emphasis on metabolism, and review the recent data that implicate several neuroendocrine and inflammatory mechanisms mobilized during chronic stress in the development of the metabolic complications that characterize central obesity and the metabolic syndrome.
The stress system coordinates the adaptive responses of the organism to stressors of any kind.
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“Stress” is defined as a state of disharmony or threatened homeostasis. The concepts of stress and ...homeostasis can be traced back to ancient Greek history, however, the integration of these notions with related physiologic and pathophysiologic mechanisms and their association with specific illnesses are much more recent.
In the present overview, we focus on the cellular and molecular infrastructure of the physiologic and behavioral adaptive responses to stress and we define the pathophysiologic effects of the dysregulation of the stress response, which may result in vulnerability to several disease entities, such as anxiety or depression and chronic inflammatory processes.
The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus–norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary–adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic β-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic–pituitary–adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and β-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5′ deiodinase, which converts the relatively inactive tetraiodothyronine (T
4) to triiodothyronine (T
3), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing “low turnover” osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (
immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
Low/moderate alcohol consumption seems to be protective against cardiovascular disease (CVD). This study aimed to investigate the association of wine/beer consumption with the 10-year CVD incidence.
...During 2001-2002, 3042 CVD-free adults consented to participate in the ATTICA study; of them 2583 completed the 10-year follow-up (85% participation rate), but precise information about fatal/nonfatal CVD incidence (myocardial infarction, angina pectoris, cardiac ischemia, heart failure, chronic arrhythmias, and stroke) was available in 2020 participants (overall retention rate 66%). Alcohol/ethanol intake and the alcoholic beverages consumed were assessed; participants were categorized into three groups (no use; ≤1 glass/week; >1 glass/week).
Alcohol drinking was reported by 56% of the participants who did not develop a CVD event and 49% of those who had (p = 0.04); whereas ethanol intake was 14 ± 16 g among those who did not had an event vs. 21 ± 18 g among those who had a CVD event (p < 0.001). A strong inverse and similar association between low wine/beer intake (≤1 glass/week) and the risk of developing CVD was observed HR: 0.40, 95% confidence interval (CI): 0.17-0.98; and HR: 0.43, 95% CI: 0.20-0.93, respectively, as compared to abstention. No significant association was found in participants exceeding drinking 1 glass/week compared with abstainers. Compared to <2 g/day ethanol intake, participants who reported 2-10, 10-20, and >20 g/day had CVD-risk HRs (95% CI) of 0.60 (0.40-0.98), 1.22 (0.60-1.14), and 1.81 (0.70-4.61), respectively.
This study revealed similar results of low wine/beer consumption against CVD incidence, mainly due to its implication on low-grade chronic inflammation.
Stress, defined as a state of threatened homeostasis, mobilizes a complex spectrum of adaptive physiologic and behavioral responses that aim to re-establish the challenged body homeostasis. The ...hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) constitute the main effector pathways of the stress system, mediating its adaptive functions. In western societies, indices of stress correlate with increasing rates of both obesity and metabolic syndrome which have reached epidemic proportions. Recent data indicate that chronic stress, associated with mild hypercortisolemia and prolonged SNS activation, favors accumulation of visceral fat and contributes to the clinical presentation of visceral obesity, type 2 diabetes, and related cardiometabolic complications. Reciprocally, obesity promotes a systemic low-grade inflammation state, mediated by increased adipokine secretion, which can chronically stimulate the stress system.
The prevalence of obesity is rising progressively, even among older age groups. By the year 2030–2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and ...older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m2. Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity – a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone – is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.
Abstract Background/ Objectives The aim of the present work was to evaluate the association between the inflammatory potential of the diet and the 10-year cardiovascular disease (CVD) incidence in ...the ATTICA Study, and whether this is modified by baseline the presence or absence of metabolic syndrome (MetS). Methods During 2001-2002, 3042 healthy adults (1514 men and 1528 women) living in the greater area of Athens were voluntarily recruited to the ATTICA study. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD event was recorded using WHO-ICD-10 criteria and MetS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised) definition. A proxy dietary anti-inflammatory index (D-AII) score computed using participants’ diet records. Results The 10-year fatal or non-fatal CVD event rate was 157 cases / 1000 participants. After adjusting for several confounding factors, an anti-inflammatory diet, as expressed by higher DII scores, was borderline associated with 10-year CVD incidence (OR3rd tertile vs. 1st tertile = 0.98, 95%CI: 0.96-1.01). This inverse association was also verified among participants without MetS at baseline (OR3rd tertile vs. 1st tertile = 0.97, 95%CI: 0.94-0.99), but not among participants with the MetS. Conclusions Results of the present work verified the protective effect of an anti-inflammatory diet towards the 10-year CVD incidence among participants without MetS. In contrast, the presence of MetS already at baseline seemed to impede this anti-inflammatory diet protective effect, which underlines the independent importance of MetS on CVD risk.
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