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. 2008 Jun;57(6):1536-43.
doi: 10.2337/db08-0094. Epub 2008 Mar 13.

Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and adipose tissue insulin sensitization after weight loss

Jeremy W Tomlinson  1 , Joanne Finney, Beverly A Hughes, Susan V Hughes, Paul M Stewart
Affiliations

Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and adipose tissue insulin sensitization after weight loss

Jeremy W Tomlinson et al. Diabetes. 2008 Jun.

Abstract

Objective: The epidemics of obesity, insulin resistance, and type 2 diabetes have heightened the need to understand mechanisms that contribute to their pathogenesis. Increased endogenous glucocorticoid production has been implicated based on parallels with Cushing's syndrome. We have assessed the impact of weight loss on glucocorticoid secretion and metabolism (notably 11beta-hydroxysteroid dehydrogenase type 1 and 5alpha-reductase [5alphaR] activity) and insulin sensitivity.

Research design and methods: Twenty obese volunteers were investigated before and after weight loss. Patients underwent hyperinsulinemic-euglycemic clamps with simultaneous adipose microdialysis and oral cortisone acetate administration. Changes in glucocorticoid secretion and metabolism were assessed using 24-h urine collections.

Results: Before weight loss, fat mass correlated with glucocorticoid secretion rate (total fat, r = 0.46, P < 0.05; trunk fat, r = 0.52, P < 0.05); however, glucocorticoid secretion rate was inversely related to insulin sensitivity (r = -0.51, P < 0.05). Hyperinsulinemia failed to suppress adipose tissue interstitial fluid glycerol release (180 +/- 50 micromol [basal] vs. 153 +/- 10 micromol [steady state], NS). After oral cortisone (25 mg), cortisol concentrations within adipose interstitial fluid increased (4.3 +/- 1.1 vs. 14.2 +/- 2.6 nmol/l, P < 0.01), but glycerol concentrations did not change. After weight loss, insulin sensitivity increased. Consistent with insulin sensitization, adipose tissue interstitial fluid glycerol concentrations fell under hyperinsulinemic conditions (186 +/- 16 vs. 117 +/- 9 micromol, P < 0.05). Glucocorticoid secretion decreased (11,751 +/- 1,520 vs. 7,464 +/- 937 microg/24 h, P < 0.05) as did 5alphaR activity (5alpha-tetrahydrocortisol-to-tetrahydrocortisol ratio 1.41 +/- 0.16 vs. 1.12 +/- 0.17, P < 0.005).

Conclusions: Obesity is associated with insulin resistance within adipose tissue and increased cortisol secretion rates; both are reversed with weight loss. Reduced 5alphaR activity after weight loss may decrease hypothalamo-pituitary-adrenal axis activation and reduce glucocorticoid metabolite production.

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Figures

Figure 1
Figure 1
A schematic representation of the hyperinsulinemic euglycemic clamp protocol with cortisone administration and simultaneous adipose tissue microdialysis. Timing of samples taken for measurement of serum insulin (*) and cortisol and cortisone (†) are shown. Throughout the clamp, blood samples were also taken every 5 minutes for measurement of blood glucose.
Figure 2
Figure 2
Total GC secretion rate correlates positively with trunk (closed circles) and total fat mass (open triangles) in 20 health obese individuals before weight loss (A) and inversely correlate with insulin sensitivity as measured by hyperinsulinemic euglycemic clamp (B).
Figure 3
Figure 3
Adipose tissue microdialysate analysis in 14 obese individuals before (open squares) and after weight loss (closed circles), under basal and hyperinsulinemic conditions. Hyperinsulinemia increased interstitial fluid pyruvate (A) and lactate (B) concentrations equally before and after weight loss. Glucose concentrations were unaltered consistent with successful clamping of blood glucose levels and were also similar before and after weight loss. Glycerol concentrations failed to suppress prior to weight loss in keeping with adipose tissue insulin resistance, but fell significantly after weight loss († p<0.05 vs. baseline before weight loss; § p<0.05 vs. baseline after weight loss; * p<0.05 before vs. after weight loss. Arrow denotes administration of cortisone acetate 25mg orally).
Figure 4
Figure 4
Serum (A) and adipose tissue interstitial fluid (B) cortisol generation, and the ratio of interstitial fluid cortisol to serum cortisol (C) following oral cortisone acetate (25mg) administration in 14 obese individuals before (open squares) and after weight loss (closed circles) († p<0.05 vs. baseline before weight loss; § p<0.05 vs. baseline after weight loss).
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References

    1. World Health Orgaization. [accessed January 2008]; web site http://www.who.int/en/
    1. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341:427–434. - PubMed
    1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122:481–486. - PubMed
    1. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17:961–969. - PubMed
    1. Fraser R, Ingram MC, Anderson NH, Morrison C, Davies E, Connell JM. Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension. 1999;33:1364–1368. - PubMed

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