Hormonal regulation of human leptin in vivo: effects of hydrocortisone and insulin

Abstract

OBJECTIVE: To investigate the effects of continuous i.v. infusion of hydrocortisone or insulin on leptin secretion in humans. SUBJECTS: Six, nonfasting healthy adults (four women, two men), aged (mean AE s.e.m.) 36.6 AE 1.7 y; body mass index (BMI) 27.6 AE 0.9 kgam 2 . DESIGN: Randomized, placebo-controlled, cross-over study, with a 2-week`wash-out' period. INTERVENTIONS: Intravenous infusion of hydrocortisone (3.3 m mga(kg min)), insulin (1 mUa(kg min)) or normal saline (placebo) for 24 h. MEASUREMENTS: Blood sampling every 1 ± 2 h for measurement of glucose, insulin, cortisol and leptin; subcutaneous abdominal fat biopsy for determination of leptin mRNA expression. RESULTS: Plasma cortisol increased to 50.0 AE 0.4 m mgadl during hydrocortisone infusion, but was unaltered during saline or insulin infusion. The plasma insulin levels were: 28.5 AE 4.7 m mUaml (placebo), 40.8 AE 9.2 m mUaml (hydrocortisone, P 0.214), and 243 AE 23.0 m mUaml (insulin, P 0.0002). Peak hyperleptinemia occurred after 16 h of insulin and 20 h of hydrocortisone infusion; peakabaseline plasma leptin levels (ngaml) were 18.2 AE 4.2a15.1 AE 3.3 (placebo, P 0.056), 42.1 AE 7.0a16.0 AE 3.8 (hydrocortisone, 163%, P 0.008) and 30.2 AE 4.3a16.6 AE 2.7 (insulin, 83%, P 0.024). Adipocyte leptin mRNA increased by 350% after the hydrocortisone infusion. CONCLUSION: Hydrocortisone, a natural glucocorticoid, induces hyperleptinemia in vivo, with a potency greater than that of insulin. The interaction between glucocorticoids and leptin may be of metabolic signi®cance in humans.

Different Relationship Between Anthropometric Markers and Umbilical Cord Plasma Leptin in Asian and Caucasian Neonates

“…First, cortisol is known to stimulate leptin secretion both in vivo and in vitro (22,23). Second, the activity of the placental enzyme 11 ␤-hydroxysteroid dehydrogenase (EC 1.1.1.146) that actively converts cortisol to cortisone near term has been shown to be positively correlated to birth weight (40) although this was not confirmed by Rogerson et al (41).…”

“…For instance, the higher serum leptin concentrations observed in female compared with male subjects (20) as early as during the neonatal period (4,9) are not only explained by differences in body composition, but also by differences in sex steroids (1,21). Cortisol is another steroid hormone that has been shown to increase leptin secretion in vitro and in vivo (22,23). Of interest for the present study, a positive correlation between leptin and cortisol umbilical cord-blood concentrations has been reported by Maffeis et al (9), raising the possibility that endogenous cortisol secretion could stimulate leptin secretion in the perinatal period.…”

Leptin and Cardiovascular Disease

“…109 In obese women and in normal-weight subjects, dexamethasone induces plasma leptin elevations that are unrelated to body fat distribution and insulin sensitivity. 110 Indeed, metyrapone-induced inhibition of cortisol biosynthesis results in hypoleptinemia in obese subjects.…”

Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans

“…This is indicated in our model by a negative interaction between adipose tissue and the CNS. Additionally, insulin up-regulates the release of leptin after food intake in healthy rodents and humans (Boden et al 1997, Askari et al 2000, as leptin causes a negative feedback in the pancreas (Ahren & Havel 1999), as shown in Fig. 7.…”