Relationship of nonalcoholic hepatic steatosis to overnight low‐dose dexamethasone suppression test in obese individuals

Zoppini, Giacomo; Targher, Giovanni; Venturi, Cristina; Zamboni, Cristina; Muggeo, Michele

doi:10.1111/j.1365-2265.2004.02154.x

Cited by 25 publications

(19 citation statements)

References 23 publications

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“…Previously it has been shown that obese individuals [12] and overweight people with type 2 diabetes [31] with fatty liver have higher 24-h urinary free cortisol excretion with impaired dexamethasone suppression of cortisol compared with control subjects. However, the effect of fatty liver per se on cortisol metabolism is not differentiated from the effect mediated by obesity in these studies.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, it is uncertain whether abnormal cortisol regulation or metabolism is responsible for the marked insulin resistance. To date, abnormalities of cortisol regulation have been described in NAFLD, including chronic activation of the HPA axis [12][13][14][15], increased urinary excretion of cortisol, and impaired suppression of cortisol [14]. However, whether these abnormalities occur because of insulin resistance, liver fat per se, or because of the association of increased body fat with NAFLD is uncertain.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Activation of 5beta-reductase in men may contribute to altered bile acid and cholesterol metabolism in NASH. NAFLD is closely correlated with a subtle, chronic activation of the HPA axis in obese, otherwise healthy, individuals [41]. A weaker point of this study, though, is the absence of any histological liver data.…”

Section: Cortexmentioning

confidence: 96%

‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis

Lonardo

Carani

Carulli

et al. 2006

Journal of Hepatology

129

100

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“…Much has been learned about glucocorticoid action from these excess states, and they can inform about the role 11␤-HSD1 may play in driving tissue-specific glucocorticoid excess in more common and diverse disease processes. Patients with nonalcoholic fatty liver disease (NAFLD), which is often associated with obesity and type 2 diabetes, have increased cortisol metabolite excretion (77)(78)(79) and decreased suppression by dexamethasone, independent of confounding factors such as body mass index (BMI) and insulin resistance (79,80), with the degree of HPA activation positively correlated with the severity of liver histopathology (79).…”

Section: A Hpa Axis In Metabolic Diseasementioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenase 1: Translational and Therapeutic Aspects

et al. 2013

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11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) interconverts the inactive glucocorticoid cortisone and its active form cortisol. It is widely expressed and, although bidirectional, in vivo it functions predominantly as an oxoreductase, generating active glucocorticoid. This allows glucocorticoid receptor activation to be regulated at a prereceptor level in a tissue-specific manner. In this review, we will discuss the enzymology and molecular biology of 11β-HSD1 and the molecular basis of cortisone reductase deficiencies. We will also address how altered 11β-HSD1 activity has been implicated in a number of disease states, and we will explore its role in the physiology and pathologies of different tissues. Finally, we will address the current status of selective 11β-HSD1 inhibitors that are in development and being tested in phase II trials for patients with the metabolic syndrome. Although the data are preliminary, therapeutic inhibition of 11β-HSD1 is also an exciting prospect for the treatment of a variety of other disorders such as osteoporosis, glaucoma, intracranial hypertension, and cognitive decline.

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Relationship of nonalcoholic hepatic steatosis to overnight low‐dose dexamethasone suppression test in obese individuals

Abstract: These results suggest that nonalcoholic hepatic steatosis is closely correlated with a subtle, chronic activation of the HPA axis in obese, otherwise healthy, individuals.

Cited by 25 publications

References 23 publications

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

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

‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis

11β-Hydroxysteroid Dehydrogenase 1: Translational and Therapeutic Aspects

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