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)

Dataset

Description

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)

    Cite this

    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.