title: Role of beta-adrenergic receptors in the hyperphagic and hypermetabolic responses to dietary methionine restriction.
abstract: Dietary methionine restriction (MR) limits fat deposition and decreases plasma leptin, while increasing food consumption, total energy expenditure (EE), plasma adiponectin, and expression of uncoupling protein 1 (UCP1) in brown and white adipose tissue (BAT and WAT). beta-adrenergic receptors (beta-AR) serve as conduits for sympathetic input to adipose tissue, but their role in mediating the effects of MR on energy homeostasis is unclear. Energy intake, weight, and adiposity were modestly higher in beta(3)-AR(-/-) mice on the Control diet compared with wild-type (WT) mice, but the hyperphagic response to the MR diet and the reduction in fat deposition did not differ between the genotypes. The absence of beta(3)-ARs also did not diminish the ability of MR to increase total EE and plasma adiponectin or decrease leptin mRNA, but it did block the MR-dependent increase in UCP1 mRNA in BAT but not WAT. In a further study, propranolol was used to antagonize remaining beta-adrenergic input (beta(1)- and beta(2)-ARs) in beta(3)-AR(-/-) mice, and this treatment blocked >50% of the MR-induced increase in total EE and UCP1 induction in both BAT and WAT. We conclude that signaling through beta-adrenergic receptors is a component of the mechanism used by dietary MR to increase EE, and that beta(1)- and beta(2)-ARs are able to substitute for beta(3)-ARs in mediating the effect of dietary MR on EE. These findings are consistent with the involvement of both UCP1-dependent and -independent mechanisms in the physiological responses affecting energy balance that are produced by dietary MR.
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Plaisance
authors.forename: Tara M
authors.initials: TM
authors.lastname: Henagan
authors.forename: Haley
authors.initials: H
authors.lastname: Echlin
authors.forename: Anik
authors.initials: A
authors.lastname: Boudreau
authors.forename: Kasey L
authors.initials: KL
authors.lastname: Hill
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Lenard
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Hasek
authors.forename: Norman
authors.initials: N
authors.lastname: Orentreich
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gettys
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006963:Hyperphagia; D008715:Methionine / Q000172:deficiency* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D008715:Methionine