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Biochemistry (Moscow)

, Volume 83, Issue 10, pp 1279–1287 | Cite as

Inhibition of Cannabinoid Receptor 1 Can Influence the Lipid Metabolism in Mice with Diet-Induced Obesity

  • L. W. Wei
  • Z. Q. Yuan
  • M. D. Zhao
  • C. W. Gu
  • J. H. Han
  • L. Fu
Article
  • 14 Downloads

Abstract

A growing number of evidences accumulated about critical metabolic role of cannabinoid type 1 receptor (CB1), carnitine palmitoyltransferase-1 (CPT1) and peroxisome proliferator-activated receptors (PPARs) in some peripheral tissues, including adipose tissue, liver, skeletal muscle and heart. To better understand the interactions of CB1, CPT1 and PPARs in these tissues, 30 diet-induced obese (DIO) C57BL/6J male mice were obtained, weight-matched and divided into two groups (15 in each group): (i) DIO/vehicle mice (D-Veh) and (ii) DIO/SR141716 mice (D-SR) treated with SR141716 (or rimonabant, a selective CB1 receptor blocker) administered orally (10 mg/kg daily). Another 15 mice fed standard diet (STD) formed the STD/vehicle group (S-Veh). At the end of 3-week treatment, mean body weight was 28.4 ± 0.5, 36.5 ± 0.8, and 30.3 ± 1.2 g for the S-Veh, D-Veh, and D-SR group, respectively (p < 0.05; D-Veh vs. D-SR). Liver weight in the D-SR group was also decreased significantly compared to the D-Veh group (p < 0.05). Serum levels of total cholesterol, high-density lipoprotein cholesterol, leptin and adiponectin in the D-SR group were ameliorated compared to the D-Veh group (p < 0.05). Both qRT-PCR and Western blot assay revealed that CB1 expression levels were efficiently blocked by SR141716 in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscles and liver (D-SR vs. D-Veh; p < 0.05), whereas there was no significant difference between S-Veh and D-Veh mice (p > 0.05). Simultaneously with the reduction of CB1 expression in the D-SR group, the expression levels of CPT1A isoform (protein) in the liver and heart and CPT1B isoform (protein) in the SAT, VAT, liver and skeletal muscles were significantly increased (p < 0.05; D-SR vs. D-Veh). Interestingly, the CPT1A and CPT1B expression levels in heart were detected slightly. The expression levels of PPARα in the SAT, VAT, liver and skeletal muscles and PPARγ in the SAT and skeletal muscles in the D-SR group were significantly increased compared to the D-Veh mice (p < 0.05). However, the PPARβ expression level differed from that of PPARα and PPARγ. Taken together, these data indicate that the inhibition of CB1 could ameliorate lipid metabolism via the stimulation of the CPT1A and CPT1B expression in vivo. Simultaneously, the PPARα and PPARγ expression levels significantly differed compared to that of PPARβ in obesity and lipid metabolism-related disorders under blockade of CB1. Both the mechanism of the influence of CB1 inhibition on lipid metabolism in the examined tissues and the specific mechanism of PPARα, PPARγ and PPARβ involvement in lipid exchange under these conditions remain to be further elucidated.

Keywords

CB1 CPT1 PPARs obesity lipid metabolism 

Abbreviations

CB1

cannabinoid type 1 receptor

CPT1

carnitine palmitoyltransferase 1

DIO

diet-induced obese (mice)

HDL-C

high-density lipoprotein cholesterol

LDL-C

low-density lipoprotein cholesterol

PPARs

peroxisome proliferator-activated receptors

SAT

subcutaneous adipose tissue

STD

standard diet

TC

total cholesterol

TG

triglycerides

VAT

visceral adipose tissue

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • L. W. Wei
    • 1
  • Z. Q. Yuan
    • 2
  • M. D. Zhao
    • 1
  • C. W. Gu
    • 1
  • J. H. Han
    • 1
  • L. Fu
    • 1
  1. 1.Laboratory Animal CenterSouthwest Medical UniversityLuzhouChina
  2. 2.Department of Orthopaedics, The First Affiliated Hospital, Orthopaedic InstituteSoochow UniversitySuzhouChina

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