title: Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation.
abstract: Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by β2-adrenoreceptor (β2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during β2-AR stimulation using salbutamol infusion in mice (P= 0.003). β2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of β2-AR agonist on brown adipocytes. Finally, β2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively,P= 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.
authors.affiliation: Cardiac Ultrasound Laboratory and Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; DHU Ageing-Thorax-Vessel-Blood, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France;
authors.forename: Laura
authors.initials: L
authors.lastname: Ernande
authors.affiliation: Research Division, Joslin Diabetes Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Kristin I
authors.initials: KI
authors.lastname: Stanford
authors.affiliation: Cardiac Ultrasound Laboratory and Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Robrecht
authors.initials: R
authors.lastname: Thoonen
authors.affiliation: Cardiac Ultrasound Laboratory and Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Haihua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cardiac Ultrasound Laboratory and Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Maëva
authors.initials: M
authors.lastname: Clerte
authors.affiliation: Research Division, Joslin Diabetes Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.affiliation: Research Division, Joslin Diabetes Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.affiliation: Cardiac Ultrasound Laboratory and Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; marielle@crosbie.com.
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology
chemical_list: D018343:Receptors, Adrenergic, beta-2; D005947:Glucose
keywords: blood flow; brown adipose tissue; glucose uptake; perfusion; β2-adrenoreceptor agonist
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