Stress hormones: physiological stress and regulation of metabolism

doi:10.1016/j.coph.2009.08.007

Current Opinion in Pharmacology

Volume 9, Issue 6, December 2009, Pages 787-793

https://doi.org/10.1016/j.coph.2009.08.007 Get rights and content

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.

Introduction

The adaptive response to acute stress is critical for the survival of the individual. Prolongation of this response, however, as in chronic stress, can have detrimental effects on whole body metabolism and, especially, on glucose homeostasis [1^••]. Glucocorticoids and catecholamines, the principal hormonal effectors of the stress system, appear to mediate these effects over time, progressively leading to various manifestations of the metabolic syndrome. Growing evidence suggests a significant positive association between increased cortisol levels, weight gain and enhanced secretion of proinflammatory hormones and cytokines (adipokines) by adipose tissue depots. Thus, chronic hypercortisolemia may contribute to visceral fat accumulation and insulin resistance, while circulating adipokines can activate the acute phase reaction and may act as a chronic stimulus to HPA axis, thus, forming a deleterious vicious cycle [2].

This review briefly describes the stress system, highlights potential mechanisms leading to stress-related cardiometabolic disease and discusses available clinical data which link chronic stress to the development of type 2 diabetes.

Section snippets

Defining stress and the normal stress response

Stress is defined as a state of threatened homeostasis, following exposure to extrinsic or intrinsic adverse forces (stressors) [3]. In order to re-establish the disturbed equilibrium against an imposed stressor, a repertoire of physiologic and behavioral responses is rapidly mobilized, constituting the adaptive stress response. In this context, attention is enhanced and brain functions focus primarily on the perceived threat. Somatically, cardiac output and respiration are accelerated,

Central control stations and effector pathways of the stress system

The stress system is subserved by a complex neuroendocrine, cellular and molecular infrastructure, extending in the central nervous system and the periphery. The central control stations of this system are positioned strategically in the hypothalamus and the brain stem and primarily include the parvocellular corticotropin-releasing hormone (CRH) and arginine–vasopressin neurons of the paraventricular nuclei of the hypothalamus and the locus coeruleus–norerpinephrine system (central sympathetic

Endocrine and metabolic complications of chronic stress

As part of an adaptive response to stress, the activation of both the HPA axis and the SNS is programmed to be not only sufficient to restore homeostasis, but also of limited duration. From an evolutionary perspective, the ability to self-restrain adaptive stress responses is considered equally important for a successful outcome, so that the associated catabolic, antireproductive, antigrowth and immunosuppressive effects are transient and in favor of survival [3, 17]. Chronic activation of the

Obesity as a state of unremitting inflammatory stress

Obesity is now widely recognized as a chronic low-grade inflammatory state which persists for as long as the excessive body weight is maintained [31]. Recent evidence links this unremitting inflammatory stress to the pathogenesis of both type 2 diabetes and atherosclerosis [32, 33].

Cytokines and other humoral mediators of inflammation are potent activators of the central stress response, forming a feedback loop through which the immune/inflammatory system communicates with the brain [34]. IL-6

Clinical data linking chronic stress, depression and type 2 diabetes

It has been long suspected that a bi-directional relationship exists between diabetes and chronic stress disorders, such as depression. Melancholic depression provides the prototypic example of chronic hyperactivation of the stress system which can result in damaging somatic effects [1^••]. An increasing volume of evidence is now indicating that patients with depression may develop manifestations of the metabolic syndrome (e.g. visceral obesity, hypertension, dyslipidemia, and impaired glucose

Conclusion

Recent findings advocate the suspected role of chronic stress in the pathophysiology of metabolic and cardiovascular disease. Chronic activation of the HPA axis and of sympathoadrenal activity because of modern life stress, together with changes in eating habits and physical activity, is suggested to slowly but steadily lead to visceral fat accumulation in a large proportion of the population that is more genetically susceptible, fuelling the growth of the obesity and diabetes epidemics.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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Stress hormones: physiological stress and regulation of metabolism

Introduction

Section snippets

Defining stress and the normal stress response

Central control stations and effector pathways of the stress system

Endocrine and metabolic complications of chronic stress

Obesity as a state of unremitting inflammatory stress

Clinical data linking chronic stress, depression and type 2 diabetes

Conclusion

References and recommended reading

Physiol Rev

J Psychosom Res

Obes Rev

Health Psychol

Nature

J Clin Invest

J Clin Endocrinol Metab

Stress and disorders of the stress system

Nat Rev Endocrinol

Stress, visceral obesity, and metabolic complications

Ann N Y Acad Sci

The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis

JAMA

Stress, adaptation, and disease. Allostasis and allostatic load

Ann N Y Acad Sci

Endocrinology of the stress response

Annu Rev Physiol

Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin

Science

Corticotropin-releasing factor (ovine) and vasopressin exert a synergistic effect on adrenocorticotropin release in man

J Clin Endocrinol Metab

Amplitude, but not frequency, modulation of adrenocorticotropin secretory bursts gives rise to the nyctohemeral rhythm of the corticotropic axis in man

J Clin Endocrinol Metab

Ultradian, circadian, and stress-related hypothalamic-pituitary-adrenal axis activity—a dynamic digital-to-analog modulation

Endocrinology

Negative glucocorticoid receptor response elements and their role in glucocorticoid action

Curr Pharm Des

Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids

Endocr Rev

Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha

Obes Res

The role of glucocorticoid action in the pathophysiology of the Metabolic Syndrome

Nutr Metab (Lond)

Stress in the brain

Eur J Pharmacol

Essential organization of the sympathetic nervous system

Baillieres Clin Endocrinol Metab

The general adaptation syndrome and the diseases of adaptation

J Clin Endocrinol

The metabolic syndrome — a neuroendocrine disorder?

Br J Nutr

Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities

J Clin Endocrinol Metab

The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes

Int J Obes Relat Metab Disord

Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 and pathogenesis of the metabolic syndrome

J Endocrinol Invest