Major Causes of High Cortisol Levels in People Living with Obesity
Weight stigma is the most significant cause of elevated cortisol levels in people living with obesity, triggering physiological stress responses that contribute to poor metabolic health and further weight gain. 1
Psychosocial Factors Leading to Elevated Cortisol
Weight Stigma and Discrimination: Experimental studies demonstrate that exposure to weight stigma significantly increases cortisol reactivity in individuals with obesity, with effects persisting up to 19 hours after the stigmatizing event 1
Chronic Psychological Stress: People with obesity experience higher rates of chronic stress related to societal judgment, discrimination in healthcare settings, and negative self-perception, all contributing to sustained cortisol elevation 1
Depression and Anxiety: There is a bidirectional relationship between depression and obesity, with each condition increasing risk for the other, and both associated with dysregulated cortisol patterns 1
Food Insecurity and Socioeconomic Stress: Low socioeconomic status and food insecurity contribute to chronic stress in individuals with obesity, particularly affecting racial and ethnic minority populations 1
Physiological Mechanisms of Cortisol Dysregulation
Hypothalamic-Pituitary-Adrenal (HPA) Axis Overactivation: Obesity is associated with overactivation of the HPA axis, leading to increased cortisol production 2
Tissue-Specific Cortisol Metabolism: Obesity features tissue-specific dysregulation of cortisol metabolism - reduced activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the liver but enhanced activity in adipose tissue 3
Adipose Tissue Cortisol Production: Subcutaneous adipose tissue in obesity shows markedly enhanced reactivation of cortisone to cortisol, creating localized high cortisol environments that may exacerbate obesity 3
Altered Cortisol Clearance: People with obesity often show increased total cortisol metabolite excretion, suggesting altered cortisol clearance that affects circulating levels 3, 4
Metabolic Factors Contributing to Cortisol Dysregulation
Visceral Adiposity: Excess visceral adipose tissue secretes pro-inflammatory cytokines that can stimulate cortisol production and alter HPA axis function 1
Insulin Resistance: Insulin resistance, common in obesity, is linked to cortisol dysregulation through complex bidirectional mechanisms 1
Oxidative Stress: Obesity is characterized by increased oxidative stress, which has been associated with cortisol dysregulation and metabolic syndrome components 1
Free Fatty Acid Metabolism: Elevated free fatty acids in obesity may stimulate the production of reactive oxygen species, contributing to stress pathway activation and cortisol dysregulation 1
Bidirectional Relationship Between Cortisol and Obesity
Reverse Causality: Recent Mendelian randomization studies suggest a bidirectional relationship, where severe obesity (class II and III) is associated with lower morning plasma cortisol levels 5
Vicious Cycle: Weight stigma leads to increased cortisol, which promotes visceral fat accumulation and metabolic syndrome, further exacerbating obesity and exposing individuals to more stigma 1
Dietary Impact: Dietary interventions can normalize cortisol metabolism - very low calorie diets can reverse up-regulation of hepatic enzymes that metabolize cortisol, while complete starvation can acutely increase cortisol secretion 4
Clinical Implications
Cushing's-Like Features: The metabolic syndrome associated with obesity has been described as "Cushing's syndrome of the abdomen" due to similarities in clinical presentation 1
Cardiovascular Risk: Cortisol dysregulation contributes to increased cardiovascular risk in obesity through effects on blood pressure, glucose metabolism, and inflammation 1
Allostatic Load: People experiencing weight discrimination have a two-fold ten-year risk of high allostatic load compared to those who do not experience such discrimination 1
Mortality Risk: Weight discrimination is associated with nearly 60% increased mortality risk, independent of BMI, partly mediated through cortisol-related pathways 1