TY - JOUR
T1 - Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Δ6- desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial
AU - Pranger, I. G.
AU - van Raalte, D. H.
AU - Brands, M.
AU - Muskiet, M. H. A.
AU - Kema, I. P.
AU - Serlie, M. J.
AU - Diamant, M.
AU - Bakker, S. J. L.
AU - Muskiet, F. A. J.
PY - 2018
Y1 - 2018
N2 - Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity. Thirty-two healthy young males (mean ± SD age 22 ± 3 years, BMI 22.4 ± 1.7 kg/m2) were allocated to receive prednisolone 7.5 mg/day (PRED7.5; n = 12), prednisolone 30 mg/day (PRED30; n = 12), or placebo (n = 8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG. In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (p ≤ 0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (r = 0.35 and 0.50, respectively). Similar results were found in PL and TG. Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.
AB - Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity. Thirty-two healthy young males (mean ± SD age 22 ± 3 years, BMI 22.4 ± 1.7 kg/m2) were allocated to receive prednisolone 7.5 mg/day (PRED7.5; n = 12), prednisolone 30 mg/day (PRED30; n = 12), or placebo (n = 8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG. In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (p ≤ 0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (r = 0.35 and 0.50, respectively). Similar results were found in PL and TG. Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045101651&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29735021
U2 - https://doi.org/10.1016/j.plefa.2018.03.009
DO - https://doi.org/10.1016/j.plefa.2018.03.009
M3 - Article
C2 - 29735021
SN - 0952-3278
VL - 132
SP - 8
EP - 15
JO - Prostaglandins, leukotrienes and essential fatty acids
JF - Prostaglandins, leukotrienes and essential fatty acids
ER -