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Randomized Controlled Trial
. 2023 Oct;31(10):2493-2504.
doi: 10.1002/oby.23874. Epub 2023 Sep 5.

The tissue-specific metabolic effects of the PPARα agonist ciprofibrate in insulin-resistant male individuals: a double-blind, randomized, placebo-controlled crossover study

Vera H W de Wit-Verheggen  1 , Froukje Vanweert  1 , Juho Raiko  2 , Viktor Liénard  3 , Gert Schaart  1 , Anne Gemmink  1 , Emmani B M Nascimento  1 , Matthijs K C Hesselink  1 , Joachim E Wildberger  4 , Roel Wierts  4 , Peter J Joris  1 , Joel Haas  3 , David Montaigne  3 , Bart Staels  3 , Esther Phielix  1 , Patrick Schrauwen  1 , Vera B Schrauwen-Hinderling  1   4 , Tineke van de Weijer  1   4
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Randomized Controlled Trial

The tissue-specific metabolic effects of the PPARα agonist ciprofibrate in insulin-resistant male individuals: a double-blind, randomized, placebo-controlled crossover study

Vera H W de Wit-Verheggen et al. Obesity (Silver Spring). 2023 Oct.

Abstract

Objective: Insulin resistance is characterized by ectopic fat accumulation leading to cardiac diastolic dysfunction and nonalcoholic fatty liver disease. The objective of this study was to determine whether treatment with the peroxisome proliferator-activated receptor-α (PPARα) agonist ciprofibrate has direct effects on cardiac and hepatic metabolism and can improve insulin sensitivity and cardiac function in insulin-resistant volunteers.

Methods: Ten insulin-resistant male volunteers received 100 mg/d of ciprofibrate and placebo for 5 weeks in a randomized double-blind crossover study. Insulin-stimulated metabolic rate of glucose (MRgluc) was measured using dynamic 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET). Additionally, cardiac function, whole-body insulin sensitivity, intrahepatic lipid content, skeletal muscle gene expression, 24-hour blood pressure, and substrate metabolism were measured.

Results: Whole-body insulin sensitivity, energy metabolism, and body composition were unchanged after ciprofibrate treatment. Ciprofibrate treatment decreased insulin-stimulated hepatic MRgluc and increased hepatic lipid content. Myocardial net MRgluc tended to decrease after ciprofibrate treatment, but ciprofibrate treatment had no effect on cardiac function and cardiac energy status. In addition, no changes in PPAR-related gene expression in muscle were found.

Conclusions: Ciprofibrate treatment increased hepatic lipid accumulation and lowered MRgluc, without affecting whole-body insulin sensitivity. Furthermore, parameters of cardiac function or cardiac energy status were not altered upon ciprofibrate treatment.

Trial registration: ClinicalTrials.gov NCT03662984.

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References

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