The Stress Axis in Obesity and Diabetes Mellitus: An Update

Laura Gianotti,Francesco Tassone,Salvatore D’Agnano,Sara Belcastro

doi:10.3390/endocrines2030031

Laura Gianotti, Francesco Tassone + Show 2 more

Open Access

https://doi.org/10.3390/endocrines2030031

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Abstract

The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress. Prolonged stress and/or inadequate regulation of the stress system can lead to a condition of chronic hypercortisolism or, in some cases, a blunted cortisol response to stress, contributing to insulin resistance, increased adiposity and type 2 diabetes mellitus. Moreover, acute and chronic stress can exacerbate or worsen metabolic conditions by supporting an inflammatory state and a tight relationship between stress, inflammation and adipose tissue has been reported and has been a growing subject of interest in recent years. We reviewed and summarized the evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus. Furthermore, we emphasized the possible role of infectious-related stress such as SarsCov2 infection in adrenal axis dysregulation, insulin resistance and diabetes in a bidirectional link. Understanding and better defining the links between stress and obesity or diabetes could contribute to further definition of the pathogenesis and the management of stress-related complications, in which the HPA axis dysregulation has a primary role.

Highlights

The hypothalamic-pituitary-adrenal (HPA) axis is one of the main systems which, in concert with the sympathetic nervous system (SNS), is activated in acute stress situations and is defined as the stress axis [1].When chronically activated or dysregulated at central or peripheral level, it can affect the individual’s health
It should be noted that the chronic stress-induced Cushingoid phenotype may be influenced by chronic hypercortisolism, and by changes in corticosteroid-binding globulin levels, GC receptor sensitivity in peripheral tissues and by the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a key enzyme in the peripheral GC metabolism [2,3,4]
The prolonged action of cortisol is associated with an increase in abdominal adiposity, which is further determined by the concomitant endocrine alterations associated with chronic hypercortisolism, in particular the inhibition of the gonadal and somatotropic axis

Summary

Introduction

The hypothalamic-pituitary-adrenal (HPA) axis is one of the main systems which, in concert with the sympathetic nervous system (SNS), is activated in acute stress situations and is defined as the stress axis [1]. It should be noted that the chronic stress-induced Cushingoid phenotype may be influenced by chronic hypercortisolism, and by changes in corticosteroid-binding globulin levels, GC receptor sensitivity in peripheral tissues and by the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a key enzyme in the peripheral GC metabolism [2,3,4] These alterations are associated with a kind of ‘genetic programming’ of the HPA axis that occurs in the fetal and perinatal period [5], influencing the activity of this axis in adulthood and promoting the onset of OB and MS [6,7]. We emphasized the possible role of infectious-related stress, such as from SarsCov infection, in HPA axis dysregulation, insulin resistance and T2DM, in a dual inverse link

Methods

Stress and Adiposity

Hpa Axis in Obesity and Diabetes

Conclusions