PMID- 29142285
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20190715
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 15
TI  - Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates 
      inflammation and diet-induced obesity.
PG  - 15645
LID - 10.1038/s41598-017-15154-6 [doi]
LID - 15645
AB  - Obesity is characterized by chronic low-grade, systemic inflammation, altered gut 
      microbiota, and gut barrier disruption. Additionally, obesity is associated with 
      increased activity of endocannabinoid system (eCB). However, the clear connection 
      between gut microbiota and the eCB system in the regulation of energy homeostasis 
      and adipose tissue inflammation and metabolism, remains to be established. We 
      investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) 
      antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment 
      that blocks endocannabinoid activity can induce changes in gut microbiota and 
      anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, 
      inflammatory cytokines and trafficking of M1 macrophages into adipose tissue. 
      Decreased inflammatory tone was associated with a lower intestinal permeability 
      and decreased metabolic endotoxemia as evidenced by reduced plasma LPS level, and 
      improved hyperglycemia and insulin resistance. 16S rRNA metagenomics sequencing 
      revealed that CB1 blockade dramatically increased relative abundance of 
      Akkermansia muciniphila and decreased Lanchnospiraceae and Erysipelotrichaceae in 
      the gut. Together, the current study suggests that blocking of CB1 ameliorates 
      Diet-Induced Obesity and metabolic disorder by modulating macrophage inflammatory 
      mediators, and that this effect is associated with alterations in gut microbiota 
      and their metabolites.
FAU - Mehrpouya-Bahrami, Pegah
AU  - Mehrpouya-Bahrami P
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Chitrala, Kumaraswamy Naidu
AU  - Chitrala KN
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Ganewatta, Mitra S
AU  - Ganewatta MS
AUID- ORCID: 0000-0002-9465-8238
AD  - Department of Chemistry and Biochemistry, University of South Carolina, Columbia, 
      SC, USA.
FAU - Tang, Chuanbing
AU  - Tang C
AD  - Department of Chemistry and Biochemistry, University of South Carolina, Columbia, 
      SC, USA.
FAU - Murphy, E Angela
AU  - Murphy EA
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Enos, Reilly T
AU  - Enos RT
AUID- ORCID: 0000-0001-5571-4586
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Velazquez, Kandy T
AU  - Velazquez KT
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - McCellan, Jamie
AU  - McCellan J
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Nagarkatti, Mitzi
AU  - Nagarkatti M
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA.
FAU - Nagarkatti, Prakash
AU  - Nagarkatti P
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Columbia, SC, USA. prakash@mailbox.sc.edu.
LA  - eng
GR  - K01 AT007824/AT/NCCIH NIH HHS/United States
GR  - P01 AT003961/AT/NCCIH NIH HHS/United States
GR  - P20 GM103641/GM/NIGMS NIH HHS/United States
GR  - R01 AT006888/AT/NCCIH NIH HHS/United States
GR  - R01 ES019313/ES/NIEHS NIH HHS/United States
GR  - R01 MH094755/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171115
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cannabinoid Receptor Antagonists)
RN  - 0 (Cytokines)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - RML78EN3XE (Rimonabant)
SB  - IM
MH  - Adipose Tissue/metabolism/pathology
MH  - Animals
MH  - Cannabinoid Receptor Antagonists/*pharmacology
MH  - Cell Movement/drug effects
MH  - Cytokines/metabolism
MH  - Gastrointestinal Microbiome/*drug effects
MH  - Inflammation/drug therapy/metabolism/pathology
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Obesity/*drug therapy/etiology/metabolism
MH  - Receptor, Cannabinoid, CB1/*antagonists & inhibitors/metabolism
MH  - Rimonabant/*pharmacology
PMC - PMC5688117
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/17 06:00
MHDA- 2019/07/16 06:00
PMCR- 2017/11/15
CRDT- 2017/11/17 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2017/11/17 06:00 [entrez]
PHST- 2017/11/17 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2017/11/15 00:00 [pmc-release]
AID - 10.1038/s41598-017-15154-6 [pii]
AID - 15154 [pii]
AID - 10.1038/s41598-017-15154-6 [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 15;7(1):15645. doi: 10.1038/s41598-017-15154-6.