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. 2017 Aug 3;7:7191. doi: 10.1038/s41598-017-07497-x

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Ndrg1 promotes lipolysis independent of its impact on adipocyte differentiation. (A) Western blot for the indicated proteins in differentiated 3t3l1 cells transfected with control or Ndrg1 siRNA. (B) Lipogenesis rate in control siRNA and Ndrg1 siRNA transfected cells (Ndrg1 si), unstimulated (unstim.) or upon insulin (Ins.) stimulation. (C) Relative glycerol and (D) FFA levels in medium from differentiated 3t3l1 control cells or Ndrg1 siRNA-treated cells stimulated with control medium or Iso. (E) Relative glycerol levels in adipocytes differentiated from primary stroma-vascular cells isolated from subcutaneous fat pads and transfected with non-targeted control (NTC) or Ndrg1 siRNA. Each data point represents a biological replicate. Stars indicate significance for given parameters between control and Ndrg1-depleted cells. (*P < 0.05, **P < 0.01, ***P < 0.001 according to ANOVA followed by the Post hoc Tukey test). (F) Model of Ndrg1 action in adipocytes. mTORC2 activates Sgk1 kinase, which phosphorylates Ndrg1 on T346. Phosphorylated Ndrg1 increases expression of Pparγ through an unknown mechanism to promote adipogenesis and adipocyte function. In a positive feedback loop, Pparγ also promotes Ndrg1 expression and stability. Additionally, Ndrg1 promotes C/Ebpα phosphorylation, which might influence its activity.