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Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity

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Abstract

The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Tissue levels of eCBs were measured by LC-MS while expressions of genes coding for CB1 and CB2 receptors were investigated by qPCR. High-fat diet induced an increase in anandamide (AEA) levels in soleus and EDL (p < 0.02). In soleus of the HFD group, these changes were accompanied by elevated Cnr1 messenger RNA (mRNA) levels (p < 0.05). In EDL, exercise training allowed to reduce significantly this diet-induced AEA increase (p < 0.005). 2-Arachidonoylglycerol (2-AG) levels were decreased and increased by high-fat diet in SAT and EDL, respectively (p < 0.04), but not affected by exercise training. Unlike the HFD + training group, 2-AG levels in soleus were also decreased in the HFD group compared to Ctl (p < 0.04). The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

ABHD4:

α/β-Hydrolase 4

Abhd4 :

α/β-Hydrolase 4 gene

ABHD6:

α/β-Hydrolase 6

Abhd6 :

α/β-Hydrolase 6 gene

ABHD12:

α/β-Hydrolase 12

Abhd12 :

α/β-Hydrolase 12 gene

AEA:

Anandamide

CB1:

Cannabinoid receptor 1

CB2:

Cannabinoid receptor 2

Cnr1 :

Cannabinoid receptor 1 gene

Cnr2 :

Cannabinoid receptor 2 gene

Ctl:

Control group

Ctl + training:

Exercise training + standard diet group

DAGL-α:

Diacylglycerol lipase α

Dagl-α :

Diacylglycerol lipase α gene

DAGL-β:

Diacylglycerol lipase β

Dagl-β :

Diacylglycerol lipase β gene

DIO:

Diet-induced obesity

eCBs:

Endocannabinoids

ECS:

Endocannabinoid system

EDL:

Extensor digitorum longus

EDTA:

Ethylenediaminetetraacetic acid

FAAH:

Fatty acid amide hydrolase

Faah :

Fatty acid amide hydrolase gene

GDE-1:

Glycerophosphodiesterase 1

Gde-1 :

Glycerophosphodiesterase 1 gene

HFD:

High-fat diet group

HFD + training:

Exercise training + high-fat diet group

MAGL:

Monoacylglycerol lipase

Magl :

Monoacylglycerol lipase gene

MAV:

Maximal aerobic velocity

NAPE-PLD:

N-acyl phosphatidylethanolamine phospholipase D

Nape-pld :

N-acyl phosphatidylethanolamine phospholipase D gene

OEA:

N-oleylethanolamine

OGTT:

Oral glucose tolerance test

PEA:

N-palmitoyl-ethanolamine

PPAR:

Peroxisome proliferator-activated receptor

PTPN-22:

Protein tyrosine phosphatase N22

Ptpn-22 :

Protein tyrosine phosphatase N22 gene

PUFA:

Polyunsaturated fatty acids

SAT:

Subcutaneous adipose tissue

RNA:

Ribonucleic acid

mRNA:

Messenger RNA

TRPV1:

Transient receptor potential cation channel subfamily V member 1

Trpv1 :

Transient receptor potential cation channel subfamily V member 1 gene

VAT:

Visceral adipose tissue

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Acknowledgments

The authors thank P. Barbez, E. Leclair, and J. Gamain for their advices and technical assistances.

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Authors and Affiliations

  1. Univ Lille - EA 7369, URePSS - Unité de Recherche Pluridisciplinaire Sport, Santé, Société - Equipe Activité Muscle, Santé, Eurasport, 413 rue Eugène Avinée, 59120, Loos, France

    François-Xavier Gamelin, Julien Aucouturier, Melissa Leriche, Erwan Dupont, Caroline Cieniewski-Bernard, Valérie Montel, Bruno Bastide & Elsa Heyman

  2. CNR, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, 80078, Pozzuoli, Italia

    Fabio Arturo Iannotti, Fabiana Piscitelli, Enrico Mazzarella, Teresa Aveta & Vincenzo Di Marzo

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  1. François-Xavier Gamelin
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  2. Julien Aucouturier
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  3. Fabio Arturo Iannotti
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  11. Bruno Bastide
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  12. Vincenzo Di Marzo
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Correspondence to François-Xavier Gamelin.

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This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Vincenzo Di Marzo and Elsa Heyman share the senior authorship.

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Gamelin, FX., Aucouturier, J., Iannotti, F.A. et al. Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity. J Physiol Biochem 72, 183–199 (2016). https://doi.org/10.1007/s13105-016-0469-5

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