Interactions Between the Stimulated Hypothalamic‐Pituitary‐Adrenal Axis and Leptin in Humans

Abstract

Leptin, produced by adipocytes, has homeostatic effects on body fat mass through inhibition of appetite and stimulation of the sympathetic nervous system. Several studies have reported that high-dose exogenous glucocorticoids increase circulating leptin concentrations in humans. Conversely, leptin has inhibitory effects on the hypothalamic-pituitary-adrenal (HPA) axis, both at the hypothalamic and adrenal levels. We hypothesized that acute hypercortisolism, in the physiological range, may not alter leptin secretion. Four stimuli of the HPA axis were administered to eight healthy male volunteers in a placebo-controlled study. On separate afternoons, in a randomised order, fasting subjects received i.v. injections of saline, naloxone (125 microg/kg); vasopressin (0.0143 IU/kg); naloxone and vasopressin in combination; or insulin (0.15 U/kg; a dose sufficient to induce hypoglycaemia). Plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol and leptin were measured before and for 120 min after the injection. The cortisol secretory response was greatest after insulin-hypoglycaemia, this response was significantly greater than that following naloxone, naloxone/vasopressin, or vasopressin alone. Despite the cortisol release, leptin concentrations were not increased after any stimulus. Insulin-hypoglycaemia was associated with a decrease in leptin concentration at 60 and 90 min, while naloxone did not alter leptin concentrations. However, basal leptin concentrations were positively correlated with integrated ACTH and cortisol responses to naloxone, but did not correlate with ACTH or cortisol responses to the other stimuli. Thus acute elevations of plasma cortisol, in the physiological range, do not appear to influence plasma leptin concentrations. The fall in plasma leptin concentration after insulin-induced hypoglycaemia may reflect catecholamine secretion after this stimulus.

Food Intake-Induced Leptin Secretion Modulates Hypothalamo-Pituitary-Adrenal Axis Response and Hypothalamic Ob-Rb Expression to Insulin Administration

“…However, in a very recent study in human, insulin-induced hypoglycemia was associated with a decrease in leptin concentration at 60 and 90 min [37]. In the present study we found that 24-hour fasting mice injected with insulin displayed a significant increase in plasma leptin levels 45 min posttreatment.…”

Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis

“…But these authors did not measure food intake, and it remains unknown whether GC-induced hyperleptinemia is followed by anorexia in humans. Moreover, acute elevation of plasma GCs, in a physiological range, induced with central pharmacological or physiological stimuli (stress, naloxone, vasopressin and/or CRH) does not appear to influence plasma leptin concentrations in humans (Nye et al, 2000;Tataranni et al, 1997) and adipose leptin gene expression in rats (Rybkin et al, 1997). Thus, further studies are required to determine whether GCs can inhibit food intake during stress by stimulating plasma leptin levels (Leal-Cerro et al, 2001).…”

Neural Substrates Underlying Interactions between Appetite Stress and Reward

“…An increased sensitivity of the HPA axis has also been observed in the leptin-receptor deficient Zucker rat [51]. Glucocorticoids may have a reciprocal effect on circulating leptin levels, inhibiting levels in some human studies [52,] but not in others [53]. In contrast to data showing an inhibitory effect of leptin on the stress response, lean humans generally show a reduced a HPA axis activation to various stressors compared to overweight individuals (who are likely to have higher plasma leptin levels than lean subjects).…”