Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men

Summary Background  The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion. Objective  To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well-known activator of the HPA axis at suprapituitary level. Design  Exercise tests on a bicycle ergometer during infusion of a lipid-heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0·9%) (control test). Setting  Department of Cardiology at the University-Hospital. Subjects  Seven healthy male subjects aged 25–33 years. Interventions  On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min. Main outcome measures  Circulating ACTH/cortisol levels and physiological variables during physical exercise. Results  FFA levels (0·4 ± 0·1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2·7 ± 1·0 mEq/l) during LHE infusion. Neither basal nor exercise-induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0·001; experimental test: 28·5% and 18·6%, P < 0·05 higher than baseline, respectively). Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0·002 and at 30 min P < 0·05 for ACTH; at 20 min P < 0·05 and at 30 min, 40 min and 50 min P < 0·001 for cortisol). Conclusions  These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH-induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.