TY - JOUR
T1 - The tissue-specific metabolic effects of the PPARa agonist ciprofibrate in insulin-resistant male individuals
T2 - a double-blind, randomized, placebo-controlled crossover study
AU - de Wit-Verheggen, Vera H W
AU - Vanweert, Froukje
AU - Raiko, Juho
AU - Liénard, Viktor
AU - Schaart, Gert
AU - Gemmink, Anne
AU - Nascimento, Emmani B M
AU - Hesselink, Matthijs K C
AU - Wildberger, Joachim E
AU - Wierts, Roel
AU - Joris, Peter J
AU - Haas, Joel
AU - Montaigne, David
AU - Staels, Bart
AU - Phielix, Esther
AU - Schrauwen, Patrick
AU - Schrauwen-Hinderling, Vera B
AU - van de Weijer, Tineke
PY - 2023/10
Y1 - 2023/10
N2 - 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-a (PPARa) 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 F-fluorodeoxyglucose-positron emission tomography ( 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.
AB - 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-a (PPARa) 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 F-fluorodeoxyglucose-positron emission tomography ( 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.
U2 - 10.1002/oby.23874
DO - 10.1002/oby.23874
M3 - Article
SN - 1930-7381
VL - 31
SP - 2493
EP - 2504
JO - Obesity
JF - Obesity
IS - 10
ER -