The ER-Associated Degradation Adapter Protein Sel1L Regulates Triglyceride Metabolism via Lipoprotein Lipase

  • Haibo Sha (Creator)
  • Adams Francisco (Creator)
  • Shengyi Sun (Creator)
  • Nicole Ehrhardt (Creator)
  • Zhen Xue (Creator)
  • Lei Liu (Creator)
  • Peter Lawrence (Creator)
  • Frits Mattijssen (Creator)
  • Robert Gruber (Creator)
  • Muhammad S. Panhwar (Creator)
  • J.T. Brenna (Creator)
  • Hang Shi (Creator)
  • Bingzhong Xue (Creator)
  • Sander Kersten (Creator)
  • André Bensadoun (Creator)
  • Miklòs Péterfy (Creator)
  • Qiaoming Long (Creator)
  • Ling Qi (Creator)



Sel1L is an adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum-associated degradation (ERAD), but its physiological role in a cell-type-specific manner remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Mechanistically, our data demonstrate a critical requirement of Sel1L for the secretion of lipoprotein lipase (LPL), independently of its role in Hrd1-mediated ERAD and ER homeostasis. Further biochemical analyses revealed that Sel1L physically interacts and stabilizes the LPL maturation complex consisted of LPL and lipase-maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER and prone to the formation of protein aggregates, which are degraded by autophagy-mediated degradation. The Sel1L-mediated control of LPL secretion is seen in other LPL-expressing cell types as well such as cardiac muscle and macrophages. Thus, our study reports a novel role of Sel1L in LPL secretion and systemic lipid metabolism.
Date made available18 May 2015
PublisherWageningen University

Research Output

The ER-Associated Degradation Adaptor Protein Sel1L Regulates LPL Secretion and Lipid Metabolism

Sha, H., Sun, S., Francisco, A., Ehrhardt, N., Xue, Z. Q., Liu, L., Mattijssen, F. B. J. & Kersten, A. H., 2014, In : Cell Metabolism. 20, 3, p. 458-470

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 42 Citations (Scopus)

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    Sha, H. (Creator), Francisco, A. (Creator), Sun, S. (Creator), Ehrhardt, N. (Creator), Xue, Z. (Creator), Liu, L. (Creator), Lawrence, P. (Creator), Mattijssen, F. (Creator), Gruber, R. (Creator), Panhwar, M. S. (Creator), Brenna, J. T. (Creator), Shi, H. (Creator), Xue, B. (Creator), Kersten, S. (Creator), Bensadoun, A. (Creator), Péterfy, M. (Creator), Long, Q. (Creator), Qi, L. (Creator) (18 May 2015). The ER-Associated Degradation Adapter Protein Sel1L Regulates Triglyceride Metabolism via Lipoprotein Lipase. Wageningen University.