Format

Send to

Choose Destination
Cell. 2015 Sep 24;163(1):84-94. doi: 10.1016/j.cell.2015.08.055.

Sympathetic neuro-adipose connections mediate leptin-driven lipolysis.

Author information

1
Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
2
Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
3
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.
4
Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10021, USA.
5
Department of Radiology, Weill Cornell Medical College, New York, NY 10021, USA.
6
Advanced Microscopy Unit, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
7
Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal. Electronic address: dominan@igc.gulbenkian.pt.

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.

PMID:
26406372
DOI:
10.1016/j.cell.2015.08.055
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center