Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Abstract

Context: Adrenal and extra-adrenal cortisol production may be involved in the development of metabolic syndrome (MetS). Objective: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the expression of HSD11B1, nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptors) a (NR3C1a) and b (NR3C1b) in the liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of severely obese patients with and without MetS. Methods: The study included 37 severely obese patients (BMI R40 kg/m 2 ), 19 with MetS (MetSC group) and 18 without (MetSK group), studied before and during bariatric surgery. Before the day of surgery, urinary free cortisol (UFC) and diurnal variation of serum and salivary cortisol were estimated. During surgery, biopsies of the liver, VAT and SAT were obtained. The expression of HSD11B1, NR3C1a and NR3C1b was evaluated by RT-PCR.Results: UFC and area under the curve for 24-h profiles of serum and salivary cortisol were lower in the MetSK group. In the MetSK group, mRNA levels of HSD11B1 in liver exhibited a negative correlation with liver NR3C1a (LNR3C1a) and VAT expression of HSD11B1 was lower than the MetSC group. Conclusions: We observed a downregulation of the NR3C1a expression and lower VAT mRNA levels of HSD11B1 in the MetSK group, indicating a lower selective tissue cortisol production and action that could protect these patients from the metabolic consequences of obesity. In the MetSK group, a lower activity of the HPA axis was also detected. Taken together, cortisol in tissue and systematic level might play a role in the development of MetS in severely obese patients.

In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with Aging: A Meta-Analysis of Clinical Studies

“…In females, follicular or luteal phase of the menstrual cycle, as well as pre- or post-menopausal status are also known to influence the HPA axis activity [33, 56, 57]. Importance of such additional determining factors that may influence peripheral cortisol release, independently of visceral obesity, are emphasized by previous clinical findings [9, 31]. These previous studies report that higher cortisol levels appear to induce metabolic syndrome in people suffering of severe visceral obesity, whereas similarly obese individuals with low cortisol output do not show characteristics of metabolic syndrome [9, 31].…”

“…Importance of such additional determining factors that may influence peripheral cortisol release, independently of visceral obesity, are emphasized by previous clinical findings [9, 31]. These previous studies report that higher cortisol levels appear to induce metabolic syndrome in people suffering of severe visceral obesity, whereas similarly obese individuals with low cortisol output do not show characteristics of metabolic syndrome [9, 31]. Thus, high cortisol output appears to aggravate complications of obesity.…”

Exogenous administration of chronic corticosterone affects hepatic cholesterol metabolism in broiler chickens showing long or short tonic immobility

“…In humans, excess cortisol secretion is related to obesity and many metabolic diseases (Abraham et al, 2013;Constantinopoulos et al, 2015). In Syrian hamsters, chronic glucocorticoid exposure can dosedependently increase plasma cholesterol and triglyceride (TG) and hepatic TG content (Solomon et al, 2011).…”

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing’s syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing’s syndrome)

“…Glycemic fluctuations do not have a major correlation with salivary cortisol excretion in diabetes mellitus (51). A concept of 'tissue-specific' Cushing's syndrome has been suggested in patients with obesity, the metabolic syndrome and insulin resistance suggesting that increased adipose expression of 11-β-hydroxysteroid dehydrogenase 1 may generate increased tissue cortisol levels (52). Subtle abnormalities in HPA axis function in diabetic patients with poor glycemic control should be interpreted with caution.…”