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

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.

Bibliographic Details

Main Authors:	Sha, Haibo, Francisco, Adams, Sun, Shengyi, Ehrhardt, Nicole, Xue, Zhen, Liu, Lei, Lawrence, Peter, Mattijssen, Frits, Gruber, Robert, Panhwar, Muhammad S., Brenna, J.T., Shi, Hang, Xue, Bingzhong, Kersten, Sander, Bensadoun, André, Péterfy, Miklòs, Long, Qiaoming, Qi, Ling
Format:	Dataset biblioteca
Published:	Wageningen University
Subjects:	Mus musculus,
Online Access:	https://research.wur.nl/en/datasets/the-er-associated-degradation-adapter-protein-sel1l-regulates-tri
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