Stress-induced alterations in estradiol sensitivity increase risk for obesity in women

Abstract

The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity exclusively in females.

Protective Effects of Hydrogen against Low‐Dose Long‐Term Radiation‐Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice

“…Body weight is an indicator that can reflect the general condition of individuals. Meanwhile, overweight is regarded as a signal of being under stress [ 29 ]. Thus, we investigated the body weight gain consecutively throughout the experiment.…”

“…This was consistent with our OFT results which showed an antianxiety effect of H 2 as well. As a well-known stressor, radiation of higher level (1 Gy or 2 Gy dose group in this study) can activate a series of in vivo responses including hormone alterations [ 29 , 30 ] and ROS increase. H 2 may normalize the body weight by adjusting the unbalanced hormone distribution or selectively scavenging the harmful ROS [ 5 ], but the concrete mechanism remains to be explored.…”

Posttraumatic stress disorder: A metabolic disorder in disguise?

“…(B) Pathology: heightened sympathetic drive (increased norepinephrine and decreased HRV) and dysregulation of the stress axis can lead to impaired GC-immune feedback such that inflammation is increased in the presence of GC resistance (Horowitz and Zunszain, 2015). The increase in GCs in this pathological state increases NPY levels, facilitates food intake and promotes lipogenesis (Michopoulos, 2016), thus further increasing inflammation that can no longer be inhibited by GC negative feedback. These downstream consequences of augmented inflammation also lead to hyperglycemia, and leptin and insulin resistance.…”

Depression and obesity: can the cycle be broken?

“…The mechanism for this is thought to be mediated by increased cortisol and repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis (Torres 2007). Excess glucocorticoids have been linked to insulin resistance, leading to leptin resistance, and leptin is part of the satiety signal pathways (Michopoulos 2016). This glucocorticoid effect therefore links leptin to the stress response.…”