title: Effect of beta1- and beta2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans.
abstract: In humans, beta-adrenergic stimulation increases energy and fat metabolism. In the case of beta1-adrenergic stimulation, it is fueled by an increased lipolysis. We examined the effect of beta2-adrenergic stimulation, with and without a blocker of lipolysis, on thermogenesis and substrate oxidation. Furthermore, the effect of beta1-and beta2-adrenergic stimulation on uncoupling protein 3 (UCP3) mRNA expression was studied. Nine lean males received a 3-h infusion of dobutamine (DOB, beta1) or salbutamol (SAL, beta2). Also, we combined SAL with acipimox to block lipolysis (SAL+ACI). Energy and substrate metabolism were measured continuously, blood was sampled every 30 min, and muscle biopsies were taken before and after infusion. Energy expenditure significantly increased approximately 13% in all conditions. Fat oxidation increased 47 +/- 7% in the DOB group and 19 +/- 7% in the SAL group but remained unchanged in the SAL+ACI condition. Glucose oxidation decreased 40 +/- 9% upon DOB, remained unchanged during SAL, and increased 27 +/- 11% upon SAL+ACI. Plasma free fatty acid (FFA) levels were increased by SAL (57 +/- 11%) and DOB (47 +/- 16%), whereas SAL+ACI caused about fourfold lower FFA levels compared with basal levels. No change in UCP3 was found after DOB or SAL, whereas SAL+ACI downregulated skeletal muscle UCP3 mRNA levels 38 +/- 13%. In conclusion, beta2-adrenergic stimulation directly increased energy expenditure independently of plasma FFA levels. Furthermore, this is the first study to demonstrate a downregulation of skeletal muscle UCP3 mRNA expression after the lowering of plasma FFA concentrations in humans, despite an increase in energy expenditure upon beta2-adrenergic stimulation.
authors.affiliation: NUTRIM, Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. j.hoeks@hb.unimaas.nl
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
authors.forename: Marleen A
authors.initials: MA
authors.lastname: van Baak
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: Gabby B
authors.initials: GB
authors.lastname: Hul
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005223:Fats / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D011719:Pyrazines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D013848:Thigh; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D005223:Fats; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011719:Pyrazines; D011943:Receptors, Adrenergic, beta; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D004280:Dobutamine; D005947:Glucose; C027696:acipimox; D000420:Albuterol