title: Effects of hyperlipidaemia on glucocorticoid metabolism: results of a randomized controlled trial in healthy young women.
abstract: OBJECTIVE
  It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is altered in obese individuals. Hyperlipidaemia with elevated levels of free fatty acids (FFAs) is also frequently seen in obesity and in the metabolic syndrome. We hypothesized, therefore, that hyperlipidaemia may alter the activity of the HPA axis.
  
  
  METHODS
  The effects of hyperlipidaemia, including increased circulating FFAs, on ACTH secretion and cortisol metabolism were analysed in 13 healthy young women during the early follicular phase of two subsequent cycles. We administered a 20% lipid/heparin (LHI) or a saline/heparin infusion (SHI) using a crossover design in random order for 330 min. A detailed characterization of glucocorticoid metabolism was performed by measurement of plasma ACTH, cortisol and urinary excretion rates of adrenal glucocorticoids and the glucocorticoid metabolites.
  
  
  RESULTS
  We observed that LHI-induced hyperlipidaemia elevated serum cortisol levels compared to SHI. No changes in plasma ACTH levels, daily urinary excretion rates of adrenal glucocorticoids, glucocorticoid precursors/metabolites and the calculated activities of the 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 11-, 17-, 21-hydroxylase and 11β-HSD 1 or 2 were found.
  
  
  CONCLUSIONS
  Our randomized controlled trial suggests that the adrenal sensitivity to ACTH may be enhanced by LHI-induced hyperlipidaemia in normal-weight healthy young women. This effect might contribute to the disturbances of the HPA axis described in women with abdominal obesity and impaired lipid metabolism.
authors.affiliation: Department of Endocrinology, Diabetes and Nutrition, Charite - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. knut.mai@charite.de
authors.forename: K
authors.initials: K
authors.lastname: Mai
authors.forename: F
authors.initials: F
authors.lastname: Reinecke
authors.forename: J
authors.initials: J
authors.lastname: Andres
authors.forename: T
authors.initials: T
authors.lastname: Bobbert
authors.forename: J
authors.initials: J
authors.lastname: Kraatz
authors.forename: S A
authors.initials: SA
authors.lastname: Wudy
authors.forename: M F
authors.initials: MF
authors.lastname: Hartmann
authors.forename: C
authors.initials: C
authors.lastname: Maser-Gluth
authors.forename: A F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: J
authors.initials: J
authors.lastname: Spranger
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D050356:Lipid Metabolism; D009765:Obesity / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D006493:Heparin