title: Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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 11β-HSD expression.
  
  
  METHODS
  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 11β-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.
  
  
  CONCLUSIONS
  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
  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.
authors.affiliation: University of California, Los Angeles, CA 90095, USA.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Incollingo Rodriguez
authors.affiliation: University of California, San Francisco, CA 94118, USA.
authors.forename: Elissa S
authors.initials: ES
authors.lastname: Epel
authors.affiliation: University of California, Los Angeles, CA 90095, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: White
authors.affiliation: University of California, Los Angeles, CA 90095, USA.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Standen
authors.affiliation: University of Edinburgh, Edinburgh EH1 1HT, Scotland, United Kingdom.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: University of California, Los Angeles, CA 90095, USA. Electronic address: tomiyama@psych.ucla.edu.
authors.forename: A Janet
authors.initials: AJ
authors.lastname: Tomiyama
mesh_terms: D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry
chemical_list: D006854:Hydrocortisone
keywords: 11β -HSD; Abdominal obesity; BMI; Cortisol; HPA axis; Obesity