title: Dependence of β3-adrenergic signaling on the adipokine leptin in cardiac myocytes.
abstract: β3-Adrenergic receptors (β3ARs) negatively regulate β-adrenergic signaling via nitric oxide and are dependent on the adipokine leptin for normal expression in adipocytes, thus making β3AR an attractive candidate for cross-talk with leptin in the heart. Accordingly, we tested the hypothesis that cardiac β3AR expression and function are dependent on leptin and are severely diminished in leptin-deficient ob/ob mice. Using isolated cardiac myocyte physiology studies, we found that β3AR function was significantly diminished in ob/ob myocytes and in wild-type myocytes treated with leptin antagonist. This finding was supported by quantitative PCR demonstrating markedly decreased β3AR mRNA levels in ob/ob mice. Both β3AR mRNA and function were restored in ob/ob mice after in vivo leptin repletion. We propose that diminished β3AR signaling may be the critical element to explain the direct effects of leptin on the myocardium and suggest that this work reveals a key feature in the role of leptin in obesity-related cardiac hypertrophy and heart failure.
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Larson
authors.forename: P P
authors.initials: PP
authors.lastname: Rainer
authors.forename: V L
authors.initials: VL
authors.lastname: Watts
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.forename: K L
authors.initials: KL
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Phan
authors.forename: L A
authors.initials: LA
authors.lastname: Barouch
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006333:Heart Failure / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000318:Adrenergic beta-Agonists; D020738:Leptin; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; C515447:leptin receptor, mouse