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. (May 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 132(2018)
• Page Start: 8
• Page End: 15
• Publication Date: 2018-05
• Subjects: Glucocorticoid -- Prednisolone -- Fatty acids -- Insulin sensitivity -- Hepatic DNL -- Glucose; BMI body mass index -- CE cholesteryl esters -- cTG circulating triglycerides -- D5Di Δ5 desaturase index -- D6Di Δ6 desaturase index -- DHA docosahexaenoic acid -- DNLi de novo lipogenesis index -- EPA eicosapentaenoic acid -- FPG fasting plasma glucose -- FPI fasting plasma insulin -- HOMA-IR homeostatic assessment model – insulin resistance -- NEFA non-esterified fatty acids -- OGTT oral glucose tolerance test -- PL phospholipids -- PPR product/precursor ratio -- SCDi stearoyl CoA desaturase index -- TG triglycerides; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2018.03.009
• Languages: English
• ISSNs: 0952-3278

Abstract

Highlights: Glucocorticoids increase the DNL index and SCD index in plasma of healthy young males. Glucocorticoids decrease the Δ-6 Desaturase index in plasma of healthy young males. The Glucocorticoid-induced fatty acid metabolism is related to insulin resistance. 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 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/m 2 ) 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.