title: Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans.
abstract: Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with11C-acetate and18F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans.
authors.affiliation: Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Denis P
authors.initials: DP
authors.lastname: Blondin
authors.affiliation: Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Frisch
authors.affiliation: Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada; Department of Nuclear Medicine and Radiobiology, Centre d'Imagerie Moléculaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Phoenix
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Centre d'Imagerie Moléculaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Centre d'Imagerie Moléculaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Éric E
authors.initials: ÉE
authors.lastname: Turcotte
authors.affiliation: Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Haman
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, QC G1V 4G5, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.affiliation: Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada. Electronic address: andre.carpentier@usherbrooke.ca.
authors.forename: André C
authors.initials: AC
authors.lastname: Carpentier
mesh_terms: D000085:Acetates / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002250:Carbon Radioisotopes; D003080:Cold Temperature; D005947:Glucose / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009525:Niacin / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012768:Shivering / Q000187:drug effects / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000085:Acetates; D002250:Carbon Radioisotopes; D014280:Triglycerides; D009525:Niacin; D005947:Glucose
keywords: brown adipose tissue; energy metabolism; intracellular triglyceride lipolysis; lipolysis; nonesterified fatty acid metabolism; positron emission tomography; shivering; thermogenesis