43 posts

Crosstalk Between Adipose and Lymphatics in Health and Disease

Gregory P Westcott and Evan D Rosen

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations that actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system’s role in lipid trafficking and mediating inflammation makes it a natural partner in regulating adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, whereas altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose crosstalk.

Endocrinology. 2022 Jan 1;163(1):bqab224. doi: 10.1210/endocr/bqab224.


Mesothelial cells are not a source of adipocytes in mice

Gregory P Westcott, Margo P Emont, Jin Li, Christopher Jacobs, Linus Tsai, Evan D Rosen

Visceral adipose tissue (VAT) depots are associated with the adverse metabolic consequences of obesity, such as insulin resistance. The developmental origin of VAT depots and the identity and regulation of adipocyte progenitor cells have been active areas of investigation. In recent years, a paradigm of mesothelial cells as a source of VAT adipocyte progenitor cells has emerged based on lineage tracing studies using the Wilms’ tumor gene, Wt1, as a marker for cells of mesothelial origin. Here, we show that Wt1 expression in adipose tissue is not limited to the mesothelium but is also expressed by a distinct preadipocyte population in mice and humans. We identify keratin 19 (Krt19) as a highly specific marker for the adult mouse mesothelium and demonstrate that Krt19-expressing mesothelial cells do not differentiate into visceral adipocytes. These results contradict the assertion that the VAT mesothelium can serve as a source of adipocytes.

Cell Rep. 2021 Jul 13;36(2):109388. doi: 10.1016/j.celrep.2021.109388.


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

Jin Li, Erwei Li, Rafael S Czepielewski, Jingyi Chi, Xiao Guo, Yong-Hyun Han, Daqing Wang, Luhong Wang, Bo Hu, Brian Dawes, Christopher Jacobs, Danielle Tenen, Samuel J Lin, Bernard Lee, Donald Morris, Adam Tobias, Gwendalyn J Randolph, Paul Cohen, Linus Tsai, Evan D Rosen

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.

Cell Metab. 2021 Jul 6;33(7):1449-1465.e6. doi: 10.1016/j.cmet.2021.04.019. Epub 2021 May 25.