Hormonal
In obese women, increased adipose tissue 11β-HSD1 activity regenerates cortisol locally, contributing to central obesity and insulin resistance, while impaired hepatic conversion of cortisone to cortisol leads to compensatory HPA axis activation without raising circulating cortisol levels.
For obese women, high body fat is linked to increased activity of an enzyme (11β-HSD1) in fat tissue that converts inactive cortisone into active cortisol locally. This local excess drives insulin resistance and fat accumulation, even if blood cortisol levels appear normal. Future treatments may target this specific enzyme in fat rather than just managing stress or blood cortisol levels.
In obese females increased reactivation of glucocorticoids in fat may contribute to the characteristics of the metabolic syndrome. Increased inactivation of cortisol in liver may be responsible for compensatory activation of the HPA axis.
Why this rating
Observational study with strong mechanistic data (biopsies, pharmacokinetics) in a specific population (obese women), but lacks interventional proof of causality in humans.
Source
Tissue-Specific Changes in Peripheral Cortisol Metabolism in Obese Women: Increased Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 Activity
Eva Rask et al. · The Journal of Clinical Endocrinology & Metabolism · 2002
DOI 10.1210/jcem.87.7.8661
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →