Journal article
A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue
Nature (London), Vol.583(7818), pp.839-844
07/2020
DOI: 10.1038/s41586-020-2527-y
PMID: 32699414
Abstract
Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity
, and defects in thermogenesis
and lipolysis
, 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 (BDNF
). Deletion of BDNF
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.
Details
- Title: Subtitle
- A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue
- Creators
- Putianqi Wang - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USAKen H Loh - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. hloh@rockefeller.eduMichelle Wu - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USADonald A Morgan - Department of Pharmacology, University of Iowa, Iowa City, IA, USAMarc Schneeberger - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USAXiaofei Yu - State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of ChinaJingyi Chi - Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USAChristin Kosse - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USADamian Kim - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USAKamal Rahmouni - Department of Pharmacology, University of Iowa, Iowa City, IA, USAPaul Cohen - Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USAJeffrey Friedman - Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. friedj@rockefeller.edu
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.583(7818), pp.839-844
- Publisher
- England
- DOI
- 10.1038/s41586-020-2527-y
- PMID
- 32699414
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 07/2020
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070488702771
Metrics
312 Record Views