@article{0876ed4781b5403693a0926bc9509011,
title = "Neurotensin is an anti-thermogenic peptide produced by lymphatic endothelial cells",
abstract = "The lymphatic vasculature plays important roles in the physiology of the organs in which it resides, though a clear mechanistic understanding of how this crosstalk is mediated is lacking. Here, we performed single-cell transcriptional profiling of human and mouse adipose tissue and found that lymphatic endothelial cells highly express neurotensin (NTS/Nts). Nts expression is reduced by cold and norepinephrine in an α-adrenergic-dependent manner, suggesting a role in adipose thermogenesis. Indeed, NTS treatment of brown adipose tissue explants reduced expression of thermogenic genes. Furthermore, adenoviral-mediated overexpression and knockdown or knockout of NTS in vivo reduced and enhanced cold tolerance, respectively, an effect that is mediated by NTSR2 and ERK signaling. Inhibition of NTSR2 promoted energy expenditure and improved metabolic function in obese mice. These data establish a link between adipose tissue lymphatics and adipocytes with potential therapeutic implications.",
keywords = "NTSR2, adipose tissue, lymphatic endothelial cells, neurotensin, single-cell RNA-seq, thermogenesis",
author = "Jin Li and Erwei Li and Czepielewski, {Rafael S.} and Jingyi Chi and Xiao Guo and Han, {Yong Hyun} and Daqing Wang and Luhong Wang and Bo Hu and Brian Dawes and Christopher Jacobs and Danielle Tenen and Lin, {Samuel J.} and Bernard Lee and Donald Morris and Adam Tobias and Randolph, {Gwendalyn J.} and Paul Cohen and Linus Tsai and Rosen, {Evan D.}",
note = "Funding Information: This work was supported by NSFC 32071138 and MOST 2020YFA0803600 to J.L. FA-2020-01-IBD-1 to R.S.C. NIH R01 DK120649 to P.C. DOD W81XWH-15-1-0251 and NIH 2P30DK057521 to L.T. NIH R01 DK119147 and DP1 DK1109668 to G.J.R. and RC2 DK116691, R01 DK085171, R01 DK102173, R01 DK102170, and R01 DK1113669 to E.D.R. We thank the BNORC supported Functional Genomics and Bioinformatics Core and the Energy Homeostasis Core at the BIDMC, particularly Yuchen He, June Corrigan, and Alex Banks. Conceptualization, J.L. L.T. and E.D.R.; human tissue procurement, S.L. B.L. A.T. and D.M.; investigation, J.L. E.L. X.G. L.W. D.W. R.S.C. J.C. D.T. B.H. and D.P.; analysis, J.L. C.J. B.D. and L.T.; data curation, L.T. B.D. and C.J.; writing, J.L. L.T. and E.D.R.; data visualization, L.T. J.L. E.L. C.J. R.S.C. and J.C.; funding acquisition, E.D.R.; supervision, L.T. G.J.R. P.C. and E.D.R. The authors declare no competing interests. Funding Information: This work was supported by NSFC 32071138 and MOST 2020YFA0803600 to J.L., FA-2020-01-IBD-1 to R.S.C., NIH R01 DK120649 to P.C., DOD W81XWH-15-1-0251 and NIH 2P30DK057521 to L.T., NIH R01 DK119147 and DP1 DK1109668 to G.J.R., and RC2 DK116691 , R01 DK085171 , R01 DK102173 , R01 DK102170 , and R01 DK1113669 to E.D.R. We thank the BNORC supported Functional Genomics and Bioinformatics Core and the Energy Homeostasis Core at the BIDMC, particularly Yuchen He, June Corrigan, and Alex Banks. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jul,
day = "6",
doi = "10.1016/j.cmet.2021.04.019",
language = "English",
volume = "33",
pages = "1449--1465.e6",
journal = "Cell metabolism",
issn = "1550-4131",
number = "7",
}