title: Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.
abstract: OBJECTIVE
  To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans.
  
  
  METHODS
  Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on (18)F-FDG PET/CT (n = 8) underwent a randomly allocated second (18)F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4).
  
  
  RESULTS
  We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on (18)F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not.
  
  
  CONCLUSIONS
  Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Salem
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Izzi-Engbeaya
authors.affiliation: Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Coello
authors.affiliation: Department of Computing, Imperial College London, London, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Thomas
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: E S
authors.initials: ES
authors.lastname: Chambers
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Comninos
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Department of Radiology, Imperial College NHS Healthcare Trust, London, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Win
authors.affiliation: Department of Radiology, Imperial College NHS Healthcare Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Al-Nahhas
authors.affiliation: Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.|Centre for Neuroimaging Sciences, King's College, London, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, UK.|Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: R N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Early Life Research Group, Academic Division of Child Health, Obsterics and Gynaecology, School of Medicine, Queen's Medical Centre, University Hospital, The University of Nottingham, Nottingham, UK.
authors.forename: H
authors.initials: H
authors.lastname: Budge
authors.affiliation: Early Life Research Group, Academic Division of Child Health, Obsterics and Gynaecology, School of Medicine, Queen's Medical Centre, University Hospital, The University of Nottingham, Nottingham, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Symonds
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Tan
authors.affiliation: Section of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000328:Adult; D003080:Cold Temperature; D065187:Controlled Before-After Studies; D004734:Energy Metabolism / Q000187:drug effects*; D019788:Fluorodeoxyglucose F18; D005934:Glucagon / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011897:Random Allocation; D022722:Thermogenesis / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18; D005934:Glucagon
keywords: 18F-FDG PET/CT; energy expenditure; glucagon; human brown adipose tissue; thermal imaging