A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue

Putianqi Wang, Ken H. Loh (), Michelle Wu, Donald A. Morgan, Marc Schneeberger, Xiaofei Yu, Jingyi Chi, Christin Kosse, Damian Kim, Kamal Rahmouni, Paul Cohen and Jeffrey Friedman ()
Additional contact information
Putianqi Wang: The Rockefeller University
Ken H. Loh: The Rockefeller University
Michelle Wu: The Rockefeller University
Donald A. Morgan: University of Iowa
Marc Schneeberger: The Rockefeller University
Xiaofei Yu: The Rockefeller University
Jingyi Chi: The Rockefeller University
Christin Kosse: The Rockefeller University
Damian Kim: The Rockefeller University
Kamal Rahmouni: University of Iowa
Paul Cohen: The Rockefeller University
Jeffrey Friedman: The Rockefeller University

Nature, 2020, vol. 583, issue 7818, 839-844

Abstract: Abstract Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity1, and defects in thermogenesis2 and lipolysis3, both of which are adipose tissue functions regulated by the sympathetic nervous system. However, the basis of these sympathetic-associated abnormalities remains unclear. Furthermore, chronic leptin administration reverses these abnormalities in adipose tissue, but the underlying mechanism remains to be discovered. Here we report that ob/ob mice, as well as leptin-resistant diet-induced obese mice, show significant reductions of sympathetic innervation of subcutaneous white and brown adipose tissue. Chronic leptin treatment of ob/ob mice restores adipose tissue sympathetic innervation, which in turn is necessary to correct the associated functional defects. The effects of leptin on innervation are mediated via agouti-related peptide and pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus. Deletion of the gene encoding the leptin receptor in either population leads to reduced innervation in fat. These agouti-related peptide and pro-opiomelanocortin neurons act via brain-derived neurotropic factor-expressing neurons in the paraventricular nucleus of the hypothalamus (BDNFPVH). Deletion of BDNFPVH blunts the effects of leptin on innervation. These data show that leptin signalling regulates the plasticity of sympathetic architecture of adipose tissue via a top-down neural pathway that is crucial for energy homeostasis.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2527-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7818:d:10.1038_s41586-020-2527-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2527-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().