Novel regulators of plasma lipid levels

Natalia Loaiza, Federico Oldoni, Jan A. Kuivenhoven*

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

6 Citaten (Scopus)

Samenvatting

Purpose of review

To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism.

Recent findings

Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93'' and "Wiskott-Aldrich syndrome protein and SCAR homologue'' complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway. Additionally, the transcription factors PHD1 and Bmal1 were identified to regulate LDL-C levels in mice by modulating cholesterol excretion. Important advances are reported on the relevance of two Genome Wide Association Studies hits: Reassessment of GALNT2 showed, in contrast to previous reports, that loss of GALNT2 reduces HDL-cholesterol in humans and other mammalian species, while phospholipid transfer protein was identified as an additional target of GALNT2. Tetratricopeptide repeat domain protein 39B was found to promote ubiquitination and degradation of Liver X receptor, and its deficiency increased HDL-cholesterol and cholesterol removal while also inhibiting lipogenesis in mice.

Summary

The unraveling of mechanisms how new factors modulate plasma lipid levels keep providing interesting opportunities to rationally design novel therapies to treat cardiovascular disease but also metabolic disorders.

Originele taal-2English
Pagina's (van-tot)231-240
Aantal pagina's10
TijdschriftCurrent Opinion in Lipidology
Volume28
Nummer van het tijdschrift3
DOI's
StatusPublished - jun-2017

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