Skeletal Muscle Interleukin-6 Regulates Hepatic Cytochrome P450 Expression: Effects of 16-Week High-Fat Diet and Exercise

被引:17
作者
Knudsen, Jakob G. [1 ]
Bertholdt, Laerke [1 ]
Gudiksen, Anders [1 ]
Gerbal-Chaloin, Sabine [2 ]
Rasmussen, Martin Kroyer [3 ]
机构
[1] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark
[2] Univ Montpellier, IRMB, INSERM, F-34290 Montpellier, France
[3] Aarhus Univ, Dept Food Sci, Blichers Alle 20,POB 50, DK-8830 Tjele, Denmark
关键词
detoxification; endurance training; IL-6; nuclear receptors; drug metabolism; DRUG-METABOLIZING-ENZYMES; PREGNANE-X-RECEPTOR; PRIMARY HUMAN HEPATOCYTES; GENE-EXPRESSION; MICROSOMAL METABOLISM; ACTIVATED RECEPTOR; INDUCED OBESITY; MESSENGER-RNA; BODY-WEIGHT; RAT-LIVER;
D O I
10.1093/toxsci/kfx258
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
High-fat diet (HFD) induces several changes to the pathways regulating energy homeostasis and changes the expression of the hepatic cytochrome p450 (Cyp) enzyme-system. Despite these pervious findings, it is still unclear how the effects of HFD and especially HFD in combination with treadmill running affect hepatic Cyp expression. In this study, we investigated the mRNA and protein expression of selected Cyp's in mice subjected to 16 weeks of HFD and treadmill running. To understand the regulatory mechanisms behind the exercise-induced reversion of the HFD-induced changes in Cyp expression, we used a model in which the exercise-induced myokine and known regulator of hepatic Cyp's, interleukin-6 (IL-6), were knocked out specifically in skeletal muscle. We found that HFD increased the mRNA expression of Cyp1a1 and Cyp4a10, and decreased the expression of Cyp2a4, Cyp2b10, Cyp2e1, and Cyp3a11. HFD in combination with treadmill running reversed the HFD increase in Cyp4a10 mRNA expression. In addition, we observed increased Cyp1a and Cyp3a protein expression as an effect of exercise, whereas Cyp2b expression was lowered as an effect of HFD. IL-6 effected the response in Cyp3a11 and Cyp1a expression. We observed no changes in the content of the aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, or peroxisome proliferation activator receptor alpha. In conclusion, we show that both HFD and exercise in HFD-fed animals can regulate hepatic Cyp expression and that changes in Cyp3a in response to HFD and exercise are dependent on skeletal muscular IL-6.
引用
收藏
页码:309 / 317
页数:9
相关论文
共 50 条
[1]   A short-term high fat diet increases exposure to midazolam and omeprazole in healthy subjects [J].
Achterbergh, Roos ;
Lammers, Laureen A. ;
van Nierop, Samuel ;
Klumpen, Heinz-Josef ;
Soeters, Maarten R. ;
Mathot, Ron A. A. ;
Romijn, Johannes A. .
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2016, 12 (07) :715-720
[2]   The mechanisms of action of PPARs [J].
Berger, J ;
Moller, DE .
ANNUAL REVIEW OF MEDICINE, 2002, 53 :409-435
[3]   Kaempferol Regulates the Lipid-Profile in High-Fat Diet-Fed Rats through an Increase in Hepatic PPARα Levels [J].
Chang, Chia Ju ;
Tzeng, Thing-Fong ;
Liou, Shorong-Shii ;
Chang, Yuan-Shiun ;
Liu, I-Min .
PLANTA MEDICA, 2011, 77 (17) :1876-1882
[4]   Immunological response as a source to variability in drug metabolism and transport [J].
Christensen, Hege ;
Hermann, Monica .
FRONTIERS IN PHARMACOLOGY, 2012, 3
[5]   INHIBITION OF HEPATIC DRUG-METABOLISM AND CARBON-TETRACHLORIDE TOXICITY IN FISCHER-344 RATS BY EXERCISE [J].
DAY, WW ;
WEINER, M .
BIOCHEMICAL PHARMACOLOGY, 1991, 42 (01) :181-184
[6]   DIFFERENTIAL-EFFECTS OF SWIMMING AND RUNNING ON MICROSOMAL METABOLISM IN MIDDLE-AGED AND AGED FISCHER 344 RATS [J].
DAY, WW ;
CHESKY, JA ;
WEINER, M .
MECHANISMS OF AGEING AND DEVELOPMENT, 1992, 63 (03) :275-286
[7]   Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner [J].
Ferrer, Beatriz ;
Navia, Belen ;
Giralt, Mercedes ;
Comes, Gemma ;
Carrasco, Javier ;
Molinero, Amalia ;
Quintana, Albert ;
Senaris, Rosa M. ;
Hidalgo, Juan .
BRAIN BEHAVIOR AND IMMUNITY, 2014, 40 :121-130
[8]   Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway [J].
Finn, Robert D. ;
Henderson, Colin J. ;
Scott, Claire L. ;
Wolf, C. Roland .
BIOCHEMICAL JOURNAL, 2009, 417 :43-54
[9]  
Fischer CP, 2006, EXERC IMMUNOL REV, V12, P6
[10]   THE EFFECT OF MUSCULAR EXERCISE ON THE MICROSOMAL-ENZYME SYSTEM OF THE RAT-LIVER [J].
FRENKL, R ;
GYORE, A ;
SZEBERENYI, S .
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY AND OCCUPATIONAL PHYSIOLOGY, 1980, 44 (02) :135-140