Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol

Strain, Gladys; Zumoff, Barnett; Kream, Jacob; Strain, James J.; Levin, Joseph; Fukushima, David K.

doi:10.1016/0026-0495(82)90054-3

Cited by 116 publications

(92 citation statements)

References 24 publications

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“…The current data allow interpretation of the fractional excretion of cortisol tracer in urine during continuous infusion in the steady state, and show that the most striking increase was in 5␤-reduced cortisone metabolites (Table 3). This may be the key mechanism underlying increased metabolic clearance rate for cortisol in obesity (45,46).…”

Section: Hsd1 In Obesitymentioning

confidence: 99%

Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone

et al. 2005

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11␤-Hydroxysteroid dehydrogenase type 1 (11HSD1) regenerates cortisol from cortisone within adipose tissue and liver. 11HSD1 inhibitors may enhance insulin sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is increased in subcutaneous adipose biopsies. We examined the regeneration of cortisol in vivo in obesity, and the effects of the 11HSD1 inhibitor carbenoxolone. We compared six lean and six obese men and performed a randomized, placebo-controlled crossover study of carbenoxolone in obese men. 11␤-Hydroxysteroid dehydrogenase type 1 (11HSD1) is a microsomal enzyme expressed in many tissues, including liver and adipose tissue (1). It catalyzes the regeneration of the active glucocorticoid cortisol from its inactive 11-keto metabolite cortisone. This intracellular generation of cortisol plays a key role in amplifying glucocorticoid receptor activation independently of the level of cortisol in the circulating plasma. Its potential importance is illustrated in animal models. Transgenic mice that overexpress 11HSD1 by approximately threefold selectively in adipocytes under the AP2 promoter/enhancer (2,3) develop about a twofold increase in intraadipose glucocorticoid levels despite no change in plasma levels, which are controlled by a compensatory fall in ACTH secretion. This results in central obesity together with hyperinsulinemia, hyperglycemia, hyperlipidemia, and hypertension. Mice with similar overexpression of 11HSD1 in liver under the ApoE promoter develop insulin resistance, dyslipidemia, and hypertension without obesity (4). Conversely, 11HSD1 knockout mice on a high-fat diet are protected from obesity, hyperglycemia, and dyslipidemia and redistribute fat to peripheral rather than central fat depots (5-7). Moreover, inbred rodent models of obesity and diabetes show tissue-specific dysregulation of 11HSD1 (2,8,9); most commonly, 11HSD1 is reduced in liver but increased in adipose tissue. These findings substantiate the hypothesis that increased intra-adipose glucocorticoid regeneration by 11HSD1 contributes to obesity and its metabolic complications.Whether increased 11HSD1 levels have a similar importance in human obesity and associated type 2 diabetes is controversial (10). The conventional measure of 11HSD1 is the ratio of urinary cortisol to cortisone metabolites, which is inconsistently altered in obesity (11-16) and diabetes (17)(18)(19). However, this ratio may be confounded by the activity of other enzymes (e.g., 11HSD type 2, 5␣-and 5␤-reductase) that differ in obesity, and is insensitive to the tissue-specific changes in 11HSD1 that have been observed in animals. Hepatic 11HSD1 has been assessed in humans by measuring the conversion of an oral dose of cortisone into cortisol in peripheral plasma after "first pass" metabolism, and is consistently reduced in obesity

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Section: Hsd1 In Obesitymentioning

confidence: 99%

Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone

et al. 2005

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“…37 HSD-1 converts cortisone to active cortisol, which results in detection of increased glucocorticoid levels by the liver, which in turn causes feedback inhibition of adrenal cortisol secretion. 38 This, in addition to increased cortisol excretion in obesity, 39 may explain the lower absolute levels of cortisol seen in obese people.…”

Section: Figmentioning

confidence: 99%

Hypothalamic-Pituitary-Adrenal Axis Function: Relative Contributions of Perceived Stress and Obesity in Women

Farag

Moore²,

Lovallo³

et al. 2008

Journal of Women's Health

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Objective: A range of behavioral and psychosocial factors may contribute to a chronically stimulated hypothalamic-pituitary-adrenal (HPA) axis and subsequently altered diurnal patterns. The goal of this cross-sectional study was to examine associations among diurnal cortisol levels, perceived stress, and obesity patterns. Methods: Seventy-eight women (aged 24-72 years) employed in a rural public school system completed the perceived stress scale, collected diurnal saliva samples, and underwent anthropometric assessments. Reduced peak-to-nadir cortisol values across the day were considered a sign of impairment in HPA function. A series of linear regression models determined the best predictors of diurnal cortisol variation. Results: There was a marginal linear trend in stress levels across body mass index (BMI) categories, with obese women reporting the highest levels of stress (p ϭ 0.07). Perceived stress was the only significant predictor of the degree of flattening of the diurnal cortisol curve in the sample as a whole (␤ ϭ Ϫ0.042, R 2 ϭ 0.11, F ϭ 8.6, p ϭ 0.005), indicating reduction in the normal diurnal pattern. Among overweight women (BMI ϭ 25-29.9 kg/m 2 ), stress and waist circumference combined predicted 35% of the variability in diurnal cortisol. In contrast, among obese women (BMI Ն 30 kg/m 2 ), BMI predicted 31% of the variability in diurnal cortisol (F ϭ 13.8, p ϭ 0.001), but stress was no longer significantly related to diurnal cortisol. Conclusions: Psychological stress predicts a significant portion of HPA axis functioning. In overweight women, perceived stress and waist circumference were of approximately equal importance in predicting adrenal cortisol secretion. However, among obese women, a major portion of the diurnal cortisol variation was predicted by BMI alone, not stress or waist circumference. This may help elucidate the mechanisms linking obesity to increased risk of cardiovascular disease (CVD).

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“…Although many obese individuals resemble patients with excess cortisol exposure, plasma cortisol levels in overweight and obese subjects have been found to be either similar to or lower than those in non-obese individuals, suggesting that cortisol metabolism may be altered in some overweight or obese individuals [1][2][3]. Indeed, there are differences in cortisol metabolism between obese men and women [4] according to patterns of regional body fat distribution [5].…”

Section: Introductionmentioning

confidence: 99%

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

et al. 2007

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Aims/hypothesis The regulation of cortisol metabolism in vivo is not well understood. We evaluated the relationship between cortisol metabolism and insulin sensitivity, adjusting for total and regional fat content and for non-alcoholic fatty liver disease. Materials and methods Twenty-nine middle-aged healthy men with a wide range of BMI were recruited. We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH 1-24 , unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. Results Cortisol clearance was strongly inversely correlated with insulin sensitivity (M value) (r=−0.61, p=0.002). Cortisol clearance was increased in people with fatty liver compared with those without (mean±SD: 243±10 vs 158± 36 ml/min; p = 0.014). Multiple regression modelling showed that the relationship between cortisol clearance and insulin sensitivity was independent of body fat. The relationship between fatty liver and insulin sensitivity was significantly influenced by body fat and cortisol clearance. Conclusions/interpretation Cortisol clearance is strongly associated with insulin sensitivity, independently of the amount of body fat. The relationship between fatty liver and insulin sensitivity is mediated in part by both fatness and cortisol clearance.

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Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol

Cited by 116 publications

References 24 publications

Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone

Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone

Hypothalamic-Pituitary-Adrenal Axis Function: Relative Contributions of Perceived Stress and Obesity in Women

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

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