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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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.cell.2015.08.055

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Role:
Author
ORCID:
0000-0001-8544-3318
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Role:
Author
ORCID:
0000-0003-2314-0439
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Role:
Author
ORCID:
0000-0003-0063-1825
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Role:
Author
ORCID:
0000-0002-0378-4854


Publisher:
Elsevier
Journal:
Cell More from this journal
Volume:
163
Issue:
1
Pages:
84-94
Publication date:
2015-09-24
Acceptance date:
2015-08-06
DOI:
EISSN:
1097-4172
ISSN:
0092-8674
Pmid:
26406372


Language:
English
Keywords:
Pubs id:
pubs:864447
UUID:
uuid:92f2e551-216f-4f21-a640-e9d38a1ad116
Local pid:
pubs:864447
Source identifiers:
864447
Deposit date:
2018-08-10
ARK identifier:

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