Cortisol Metabolism After Weight Loss
Cortisol Metabolism After Weight Loss
Characteristics of participants are shown in Table 1. The median weight loss 2 years after gastric bypass surgery was 44·2 kg (ranging from 15·3 to 61·7 kg). As expected, measures of obesity such as BMI, waist circumference and fat mass all decreased significantly, although subjects were still overweight with a mean BMI of 30·3 kg/m at follow-up. Five women had a BMI < 25 kg/m at follow-up (data not shown).
The glucocorticoid excretion, calculated as the sum of cortisol and cortisone metabolites (see 'Patients and methods'), decreased significantly after surgery-induced weight loss. The excretion of cortisol (i.e. THF, 5α-THF and α-cortol) and cortisone metabolites (i.e. THE and α-cortolone) both decreased significantly; however, this was also the case for the cortisol-to-cortisone metabolite ratio (Table 2). In addition, the ratio of 5α-THF/THF (Table 1) and the ratio of the testosterone metabolites androsterone/etiocholanolone diminished, the latter from 1·01 ± 0·46 to 0·70 ± 0·33, both mainly due to decreased 5α-reductase activity. The amount of glucocorticoids secreted was associated with insulin resistance and insulin level at follow-up, r = 0·439 P = 0·041 and r = 0·471 P = 0·027, respectively.
The correlations of glucocorticoid metabolites with measures of obesity before and after weight loss are shown in Table 3. Strong associations were found between abdominal obesity and the sum of glucocorticoid metabolites, in particular between cortisol metabolites and central obesity (Fig. 1).
(Enlarge Image)
Figure 1.
Cortisol and central obesity. Correlation between cortisol metabolite [THF (tetrahydrocortisol) + 5α-THF + α-cortol] excretion per day and waist circumference before weight loss. Spearman correlation coefficient r =0·565 P = 0·012.
Comparing different measures of 11β-HSD type 1, we found no correlations between its mRNA expression in subcutaneous fat before or after weight loss and glucocorticoid urinary metabolites. However, before weight loss, 11ß-HSD type 1 enzyme activity in subcutaneous abdominal fat correlated positively with excretion of the cortisol metabolites: THF, (r = 0·661 P = 0·01 at 18 h of incubation) and 5α-THF (r = 0·662 P = 0·01 at 24 h of incubation), whereas no correlations were found to visceral 11ß-HSD type 1 expression/activity. Unfortunately, there was not enough material for the analysis of enzyme activity from the subcutaneous biopsies at follow-up, so only mRNA expression data for 11ß-HSD type 1 are available from this time point.
Analysing the links between obesity and the activity of 5 α-reductase, we found correlations between androsterone excretion and weight before and after surgery (r = 0·548 P = 0·01 and r = 0,486 P = 0·01, respectively). Excretion of 5α-THF correlated with waist circumference preoperatively (r = 0·607 P = 0·006), but not at follow-up. Most correlations between obesity and the glucocorticoid metabolites before weight loss remained at follow-up, except for the correlation between cortisol/cortisone and waist circumference (Table 3).
Results
Characteristics of participants are shown in Table 1. The median weight loss 2 years after gastric bypass surgery was 44·2 kg (ranging from 15·3 to 61·7 kg). As expected, measures of obesity such as BMI, waist circumference and fat mass all decreased significantly, although subjects were still overweight with a mean BMI of 30·3 kg/m at follow-up. Five women had a BMI < 25 kg/m at follow-up (data not shown).
The glucocorticoid excretion, calculated as the sum of cortisol and cortisone metabolites (see 'Patients and methods'), decreased significantly after surgery-induced weight loss. The excretion of cortisol (i.e. THF, 5α-THF and α-cortol) and cortisone metabolites (i.e. THE and α-cortolone) both decreased significantly; however, this was also the case for the cortisol-to-cortisone metabolite ratio (Table 2). In addition, the ratio of 5α-THF/THF (Table 1) and the ratio of the testosterone metabolites androsterone/etiocholanolone diminished, the latter from 1·01 ± 0·46 to 0·70 ± 0·33, both mainly due to decreased 5α-reductase activity. The amount of glucocorticoids secreted was associated with insulin resistance and insulin level at follow-up, r = 0·439 P = 0·041 and r = 0·471 P = 0·027, respectively.
The correlations of glucocorticoid metabolites with measures of obesity before and after weight loss are shown in Table 3. Strong associations were found between abdominal obesity and the sum of glucocorticoid metabolites, in particular between cortisol metabolites and central obesity (Fig. 1).
(Enlarge Image)
Figure 1.
Cortisol and central obesity. Correlation between cortisol metabolite [THF (tetrahydrocortisol) + 5α-THF + α-cortol] excretion per day and waist circumference before weight loss. Spearman correlation coefficient r =0·565 P = 0·012.
Comparing different measures of 11β-HSD type 1, we found no correlations between its mRNA expression in subcutaneous fat before or after weight loss and glucocorticoid urinary metabolites. However, before weight loss, 11ß-HSD type 1 enzyme activity in subcutaneous abdominal fat correlated positively with excretion of the cortisol metabolites: THF, (r = 0·661 P = 0·01 at 18 h of incubation) and 5α-THF (r = 0·662 P = 0·01 at 24 h of incubation), whereas no correlations were found to visceral 11ß-HSD type 1 expression/activity. Unfortunately, there was not enough material for the analysis of enzyme activity from the subcutaneous biopsies at follow-up, so only mRNA expression data for 11ß-HSD type 1 are available from this time point.
Analysing the links between obesity and the activity of 5 α-reductase, we found correlations between androsterone excretion and weight before and after surgery (r = 0·548 P = 0·01 and r = 0,486 P = 0·01, respectively). Excretion of 5α-THF correlated with waist circumference preoperatively (r = 0·607 P = 0·006), but not at follow-up. Most correlations between obesity and the glucocorticoid metabolites before weight loss remained at follow-up, except for the correlation between cortisol/cortisone and waist circumference (Table 3).
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