title: Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice.
abstract: Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty acids (FAs). We investigated whether exposure to n-3 FA at a young age may decrease tissue endocannabinoid levels and prevent metabolic disorders induced by a later high-fat diet (HFD) challenge. Three-week-old mice received a 5% lipid diet containing lard, lard plus safflower oil, or lard plus linseed oil for 10 weeks. Then, mice were challenged with a 30% lard diet for 10 additional weeks. A low n-6/n-3 FA ratio in the early diet induces a marked decrease in liver endocannabinoid levels. A similar reduction was observed in transgenic Fat-1 mice, which exhibit high tissue levels of n-3 FA compared with wild-type mice. Hepatic expression of key enzymes involved in carbohydrate and lipid metabolism was concomitantly changed. Interestingly, some gene modifications persisted after HFD challenge and were associated with improved glycemic control. These findings indicate that early dietary interventions based on n-3 FA may represent an alternative strategy to drugs for reducing endocannabinoid tone and improving metabolic parameters in the metabolic syndrome.
authors.affiliation: Team Pathophysiology of Dyslipidemia, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Demizieux
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Team Pathophysiology of Dyslipidemia, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Troy-Fioramonti
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
authors.forename: Fabio Arturo
authors.initials: FA
authors.lastname: Iannotti
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Borrino
authors.affiliation: Team Pathophysiology of Dyslipidemia, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gresti
authors.affiliation: Team Pathophysiology of Dyslipidemia, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Muller
authors.affiliation: Team Lipid Transfer Proteins and Lipoprotein Metabolism, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bellenger
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy vdimarzo@icb.cnr.it pascal.degrace@u-bourgogne.fr.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Team Pathophysiology of Dyslipidemia, Faculty of Sciences Gabriel, INSERM UMR866 "Lipides, Nutrition, Cancer," Université de Bourgogne Franche-Comté, Dijon, France vdimarzo@icb.cnr.it pascal.degrace@u-bourgogne.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Degrace
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D050260:Carbohydrate Metabolism / Q000235:genetics; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D063388:Endocannabinoids / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D063388:Endocannabinoids; D017962:alpha-Linolenic Acid