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A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue.
- Source :
-
Nature [Nature] 2020 Jul; Vol. 583 (7818), pp. 839-844. Date of Electronic Publication: 2020 Jul 22. - Publication Year :
- 2020
-
Abstract
- Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity <superscript>1</superscript> , and defects in thermogenesis <superscript>2</superscript> and lipolysis <superscript>3</superscript> , 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 <superscript>PVH</superscript> ). Deletion of BDNF <superscript>PVH</superscript> 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.
- Subjects :
- Agouti-Related Protein metabolism
Animals
Arcuate Nucleus of Hypothalamus cytology
Arcuate Nucleus of Hypothalamus metabolism
Leptin deficiency
Lipolysis
Male
Mice
Mice, Inbred C57BL
Neurons metabolism
Pro-Opiomelanocortin metabolism
Signal Transduction
Subcutaneous Fat innervation
Subcutaneous Fat metabolism
Thermogenesis
Adipose Tissue innervation
Adipose Tissue metabolism
Brain-Derived Neurotrophic Factor metabolism
Leptin metabolism
Sympathetic Nervous System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 583
- Issue :
- 7818
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 32699414
- Full Text :
- https://doi.org/10.1038/s41586-020-2527-y