Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial

I. G. Pranger; D. H. van Raalte; M. Brands; M. H. A. Muskiet; I. P. Kema; M. J. Serlie; M. Diamant; S. J. L. Bakker; F. A. J. Muskiet

doi:10.1016/j.plefa.2018.03.009

Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial

I. G. Pranger^*, D. H. van Raalte, M. Brands, M. H. A. Muskiet, I. P. Kema, M. J. Serlie, M. Diamant, S. J. L. Bakker, F. A. J. Muskiet

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

Abstract

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 Delta 6-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/m(2)) were allocated to receive prednisolone 7.5mg/day (PRED7.5; n = 12), prednisolone 30mg/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:l omega 7/18:2 omega 6, SCDi from 16:omega)7/16:0 and D6Di from 22:6 omega)3/20:5 omega)3. 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]% (rho

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.

Original language	English
Pages (from-to)	8-15
Number of pages	8
Journal	Prostaglandins Leukotrienes and Essential Fatty Acids
Volume	132
DOIs	https://doi.org/10.1016/j.plefa.2018.03.009
Publication status	Published - May-2018

Keywords

Glucocorticoid
Prednisolone
Fatty acids
Insulin sensitivity
Hepatic DNL
Glucose
GALLUS-GALLUS-DOMESTICUS
FATTY-ACID-COMPOSITION
INSULIN-RESISTANCE
METABOLIC SYNDROME
HEPATIC LIPOGENESIS
STEROID-HORMONES
LIVER-DISEASE
LIPID CLASSES
GLUCOCORTICOIDS
DEXAMETHASONE

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Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Δ6- desaturase activity in healthy males
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Pranger, I. G., van Raalte, D. H., Brands, M., Muskiet, M. H. A., Kema, I. P., Serlie, M. J., Diamant, M., Bakker, S. J. L., & Muskiet, F. A. J. (2018). Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial. Prostaglandins Leukotrienes and Essential Fatty Acids, 132, 8-15. https://doi.org/10.1016/j.plefa.2018.03.009

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title = "Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial",

abstract = "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 Delta 6-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/m(2)) were allocated to receive prednisolone 7.5mg/day (PRED7.5; n = 12), prednisolone 30mg/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:l omega 7/18:2 omega 6, SCDi from 16:omega)7/16:0 and D6Di from 22:6 omega)3/20:5 omega)3. 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]% (rhoPrednisolone 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.",

keywords = "Glucocorticoid, Prednisolone, Fatty acids, Insulin sensitivity, Hepatic DNL, Glucose, GALLUS-GALLUS-DOMESTICUS, FATTY-ACID-COMPOSITION, INSULIN-RESISTANCE, METABOLIC SYNDROME, HEPATIC LIPOGENESIS, STEROID-HORMONES, LIVER-DISEASE, LIPID CLASSES, GLUCOCORTICOIDS, DEXAMETHASONE",

author = "Pranger, {I. G.} and {van Raalte}, {D. H.} and M. Brands and Muskiet, {M. H. A.} and Kema, {I. P.} and Serlie, {M. J.} and M. Diamant and Bakker, {S. J. L.} and Muskiet, {F. A. J.}",

year = "2018",

month = may,

doi = "10.1016/j.plefa.2018.03.009",

language = "English",

volume = "132",

pages = "8--15",

journal = "Prostaglandins Leukotrienes and Essential Fatty Acids",

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Pranger, IG, van Raalte, DH, Brands, M, Muskiet, MHA, Kema, IP, Serlie, MJ, Diamant, M, Bakker, SJL & Muskiet, FAJ 2018, 'Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial', Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 132, pp. 8-15. https://doi.org/10.1016/j.plefa.2018.03.009

Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males : A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial. / Pranger, I. G.; van Raalte, D. H.; Brands, M. et al.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 132, 05.2018, p. 8-15.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males

T2 - 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 - 2018/5

Y1 - 2018/5

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 Delta 6-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/m(2)) were allocated to receive prednisolone 7.5mg/day (PRED7.5; n = 12), prednisolone 30mg/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:l omega 7/18:2 omega 6, SCDi from 16:omega)7/16:0 and D6Di from 22:6 omega)3/20:5 omega)3. 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]% (rhoPrednisolone 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 Delta 6-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/m(2)) were allocated to receive prednisolone 7.5mg/day (PRED7.5; n = 12), prednisolone 30mg/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:l omega 7/18:2 omega 6, SCDi from 16:omega)7/16:0 and D6Di from 22:6 omega)3/20:5 omega)3. 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]% (rhoPrednisolone 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.

KW - Glucocorticoid

KW - Prednisolone

KW - Fatty acids

KW - Insulin sensitivity

KW - Hepatic DNL

KW - Glucose

KW - GALLUS-GALLUS-DOMESTICUS

KW - FATTY-ACID-COMPOSITION

KW - INSULIN-RESISTANCE

KW - METABOLIC SYNDROME

KW - HEPATIC LIPOGENESIS

KW - STEROID-HORMONES

KW - LIVER-DISEASE

KW - LIPID CLASSES

KW - GLUCOCORTICOIDS

KW - DEXAMETHASONE

U2 - 10.1016/j.plefa.2018.03.009

DO - 10.1016/j.plefa.2018.03.009

M3 - Article

C2 - 29735021

VL - 132

SP - 8

EP - 15

JO - Prostaglandins Leukotrienes and Essential Fatty Acids

JF - Prostaglandins Leukotrienes and Essential Fatty Acids

SN - 0952-3278

ER -

Pranger IG, van Raalte DH, Brands M, Muskiet MHA, Kema IP, Serlie MJ et al. Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Delta 6-desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial. Prostaglandins Leukotrienes and Essential Fatty Acids. 2018 May;132:8-15. doi: 10.1016/j.plefa.2018.03.009