Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Autor: Zhu Y; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Yao L; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Gallo-Ferraz AL; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Bombassaro B; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Simões MR; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Abe I; Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes & Metabolism, Harvard Medical School, Boston, MA, USA.; Department of Cardiology and Clinical Examination, Oita University, Faculty of Medicine, Oita, Japan., Chen J; School of Sport Science, Beijing Sport University, Beijing, China., Sarker G; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Ciccarelli A; Advanced Light Microscopy, The Francis Crick Institute, London, UK., Zhou L; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Lee C; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Sidarta-Oliveira D; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Martínez-Sánchez N; Oxford Centre for Diabetes, Endocrinology and Metabolism Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Dustin ML; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Zhan C; Department of Haematology, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Horvath TL; Department of Obstetrics/Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA., Velloso LA; Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Kajimura S; Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes & Metabolism, Harvard Medical School, Boston, MA, USA., Domingos AI; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. ana.domingos@dpag.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Oct; Vol. 634 (8032), pp. 243-250. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1038/s41586-024-07863-6
Abstrakt: Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns 1 . Here we uncover the mechanism by which NPY in sympathetic neurons 2,3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY + sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation of mural cells, which are a source of thermogenic adipocytes in both BAT and WAT 4-6 . We found that diet-induced obesity leads to neuropathy of NPY + axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapular BAT, reducing its thermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: