Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes

Hyuek Jong Lee (), Jueun Lee, Myung Jin Yang, Young-Chan Kim, Seon Pyo Hong, Jung Mo Kim, Geum-Sook Hwang () and Gou Young Koh ()
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Hyuek Jong Lee: Institute for Basic Science (IBS)
Jueun Lee: Korea Basic Science Institute
Myung Jin Yang: Institute for Basic Science (IBS)
Young-Chan Kim: Institute for Basic Science (IBS)
Seon Pyo Hong: Institute for Basic Science (IBS)
Jung Mo Kim: Institute for Basic Science (IBS)
Geum-Sook Hwang: Korea Basic Science Institute
Gou Young Koh: Institute for Basic Science (IBS)

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Active thermogenesis in the brown adipose tissue (BAT) facilitating the utilization of lipids and glucose is critical for maintaining body temperature and reducing metabolic diseases, whereas inactive BAT accumulates lipids in brown adipocytes (BAs), leading to BAT whitening. Although cellular crosstalk between endothelial cells (ECs) and adipocytes is essential for the transport and utilization of fatty acid in BAs, the angiocrine roles of ECs mediating this crosstalk remain poorly understood. Using single-nucleus RNA sequencing and knock-out male mice, we demonstrate that stem cell factor (SCF) derived from ECs upregulates gene expressions and protein levels of the enzymes for de novo lipogenesis, and promotes lipid accumulation by activating c-Kit in BAs. In the early phase of lipid accumulation induced by denervation or thermoneutrality, transiently expressed c-Kit on BAs increases the protein levels of the lipogenic enzymes via PI3K and AKT signaling. EC-specific SCF deletion and BA-specific c-Kit deletion attenuate the induction of the lipogenic enzymes and suppress the enlargement of lipid droplets in BAs after denervation or thermoneutrality in male mice. These data provide insight into SCF/c-Kit signaling as a regulator that promotes lipid accumulation through the increase of lipogenic enzymes in BAT when thermogenesis is inhibited.

Date: 2023
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DOI: 10.1038/s41467-023-38433-5

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