title: Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.
abstract: OBJECTIVE
  Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.
  
  
  METHODS
  Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally.
  
  
  RESULTS
  THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice.
  
  
  CONCLUSIONS
  Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.
authors.affiliation: Hotchkiss Brain Institute and Snyder Institute of Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nina L
authors.initials: NL
authors.lastname: Cluny
authors.affiliation: Hotchkiss Brain Institute and Snyder Institute of Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Keenan
authors.affiliation: Faculty of Kinesiology and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Raylene A
authors.initials: RA
authors.lastname: Reimer
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Hotchkiss Brain Institute and Snyder Institute of Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D059305:Diet, High-Fat; D013759:Dronabinol / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D002149:Energy Intake / Q000187:drug effects / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000382:microbiology* / Q000503:physiopathology
chemical_list: D013759:Dronabinol