Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review

Abstract

a b s t r a c tBackground: Although there is substantial evidence of differential hypothalamic-pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. Objectives: To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. Data sources: Included papers used Pubmed, Google Scholar, and the University of California Library search engines with search terms body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, sagittal diameter, abdominal versus peripheral body fat distribution, body fat percentage, DEXA, abdominal obesity, and cortisol with terms awakening response, slope, total daily output, reactivity, feedback sensitivity, long-term output, and 11␤-HSD expression. Study eligibility criteria: Empirical research papers were eligible provided that they included at least one type of obesity (general or abdominal), measured at least one relevant cortisol parameter, and a priori tested for a relationship between obesity and cortisol. Results: A general pattern of findings emerged where greater abdominal fat is associated with greater responsivity of the HPA axis, reflected in morning awakening and acute stress reactivity, but some studies did show underresponsiveness. When examined in adipocytes, there is a clear upregulation of cortisol output (due to greater expression of 11␤-HSD1), but in hepatic tissue this cortisol is downregulated. Overall obesity (BMI) appears to also be related to a hyperresponsive HPA axis in many but not all studies, such as when acute reactivity is examined. Limitations: The reviewed literature contains numerous inconsistencies and contradictions in research methodologies, sample characteristics, and results, which partially precluded the development of clear and reliable patterns of dysregulation in each investigated cortisol parameter. Conclusions and implications:The literature to date is inconclusive, which may well arise from differential effects of generalized obesity vs. abdominal obesity or from modulators such as sex, sex hormones, and chronic stress. While the relationship between obesity and adipocyte cortisol seems to be clear, further research is warranted to understand how adipocyte cortisol metabolism influences circulating cortisol levels and to establish consistent patterns of perturbations in adrenal cortisol activity in both generalized and abdominal obesity.

Adiposity moderates links from early adversity and depressive symptoms to inflammatory reactivity to acute stress during late adolescence

“…This may be due to potential opposing effects of early adversity and adiposity on HPA axis functioning. In past studies, early adversity has been associated with decreased HPA activity whereas adiposity has been associated with enhanced HPA activity, though not all studies have observed these relations (Chiang et al, 2015b; Repetti et al, 2011; Rodriguez et al, 2015). Similarly, in the present study, greater exposure to early adversity was associated with decreased total cortisol output and reactivity whereas greater WC was associated with greater HPA reactivity.…”

“…Both early adversity and depression have been associated with alterations in the HPA axis, which regulates inflammatory processes (Burke et al, 2005; Chiang et al, 2015b; Repetti et al, 2011; Rohleder, 2014). Furthermore, there is some evidence suggesting HPA functioning is dysregulated in the presence of greater adiposity (Rodriguez et al, 2015). As such, interaction effects between early adversity and depressive symptoms and adiposity may extend to the HPA axis.…”

Cortisol Stress Reactivity to the Trier Social Stress Test in Obese Adults

“…Hereby, a general correlation between the BMI and cortisol can be observed [9]. A systematic review of Incollingo Rodriguez et al [10] demonstrated that obese individuals show a greater stress-related cortisol response to laboratory acute challenges. However, the five included studies had methodological differences and limitations [9, 11-14].…”

Effects of High-fat Diets on Biochemical Profiles and Morpho- Quantitative Characteristics of C57BL/6 Mice Adrenal Glands

“…The literature, to date, is not conclusive, which could be due to the differential effects of generalized obesity against abdominal obesity or modulators such as sex, sex hormones and chronic stress (Incollingo Rodriguez et al, 2015).…”