2. Academic Validation
  3. Neurotensin is an anti-thermogenic peptide produced by lymphatic endothelial cells

Neurotensin is an anti-thermogenic peptide produced by lymphatic endothelial cells

  • Cell Metab. 2021 Jul 6;33(7):1449-1465.e6. doi: 10.1016/j.cmet.2021.04.019.
Jin Li 1,  Erwei Li 2,  Rafael S Czepielewski 3,  Jingyi Chi 4,  Xiao Guo 5,  Yong-Hyun Han 3,  Daqing Wang 2,  Luhong Wang 2,  Bo Hu 6,  Brian Dawes 2,  Christopher Jacobs 2,  Danielle Tenen 2,  Samuel J Lin 7,  Bernard Lee 7,  Donald Morris 7,  Adam Tobias 7,  Gwendalyn J Randolph 3,  Paul Cohen 4,  Linus Tsai 8,  Evan D Rosen 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai, China; Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
  • 2 Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • 3 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • 4 Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA.
  • 5 State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai, China.
  • 6 Dana-Farber Cancer Institute, Boston, MA, USA.
  • 7 Division of Plastic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • 8 Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute, Cambridge, MA, USA.
  • 9 Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute, Cambridge, MA, USA. Electronic address: [email protected].
PMID: 34038712 DOI: 10.1016/j.cmet.2021.04.019
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.

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