title: Sympathetic neuro-adipose connections mediate leptin-driven lipolysis.
abstract: Leptin is a hormone produced by the adipose tissue that acts in the brain, stimulating white fat breakdown. We find that the lipolytic effect of leptin is mediated through the action of sympathetic nerve fibers that innervate the adipose tissue. Using intravital two-photon microscopy, we observe that sympathetic nerve fibers establish neuro-adipose junctions, directly "enveloping" adipocytes. Local optogenetic stimulation of sympathetic inputs induces a local lipolytic response and depletion of white adipose mass. Conversely, genetic ablation of sympathetic inputs onto fat pads blocks leptin-stimulated phosphorylation of hormone-sensitive lipase and consequent lipolysis, as do knockouts of dopamine β-hydroxylase, an enzyme required for catecholamine synthesis. Thus, neuro-adipose junctions are necessary and sufficient for the induction of lipolysis in white adipose tissue and are an efferent effector of leptin action. Direct activation of sympathetic inputs to adipose tissues may represent an alternative approach to induce fat loss, circumventing central leptin resistance. PAPERCLIP.
authors.affiliation: Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Roksana M
authors.initials: RM
authors.lastname: Pirzgalska
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Mafalda M A
authors.initials: MM
authors.lastname: Pereira
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Nadiya
authors.initials: N
authors.lastname: Kubasova
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenue Professor Gama Pinto, Lisbon 1649-003, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Barateiro
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Seixas
authors.affiliation: Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Yi-Hsueh
authors.initials: YH
authors.lastname: Lu
authors.affiliation: Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Albina
authors.initials: A
authors.lastname: Kozlova
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Henning
authors.initials: H
authors.lastname: Voss
authors.affiliation: Advanced Microscopy Unit, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Martins
authors.affiliation: Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal. Electronic address: dominan@igc.gulbenkian.pt.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Domingos
mesh_terms: D052436:Adipose Tissue, White / Q000294:innervation / Q000378:metabolism*; D000818:Animals; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D020738:Leptin; D011943:Receptors, Adrenergic, beta