PARPs in lipid metabolism and related diseases

Magdolna Szántó, Rebecca Gupte, W. Lee Kraus, Pal Pacher, Peter Bai

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations

Abstract

PARPs and tankyrases (TNKS) represent a family of 17 proteins. PARPs and tankyrases were originally identified as DNA repair factors, nevertheless, recent advances have shed light on their role in lipid metabolism. To date, PARP1, PARP2, PARP3, tankyrases, PARP9, PARP10, PARP14 were reported to have multi-pronged connections to lipid metabolism. The activity of PARP enzymes is fine-tuned by a set of cholesterol-based compounds as oxidized cholesterol derivatives, steroid hormones or bile acids. In turn, PARPs modulate several key processes of lipid homeostasis (lipotoxicity, fatty acid and steroid biosynthesis, lipoprotein homeostasis, fatty acid oxidation, etc.). PARPs are also cofactors of lipid-responsive nuclear receptors and transcription factors through which PARPs regulate lipid metabolism and lipid homeostasis. PARP activation often represents a disruptive signal to (lipid) metabolism, and PARP-dependent changes to lipid metabolism have pathophysiological role in the development of hyperlipidemia, obesity, alcoholic and non-alcoholic fatty liver disease, type II diabetes and its complications, atherosclerosis, cardiovascular aging and skin pathologies, just to name a few. In this synopsis we will review the evidence supporting the beneficial effects of pharmacological PARP inhibitors in these diseases/pathologies and propose repurposing PARP inhibitors already available for the treatment of various malignancies.

Original languageEnglish (US)
Article number101117
JournalProgress in Lipid Research
Volume84
DOIs
StatePublished - Nov 2021

Keywords

  • ABCA1
  • ACAT1
  • ARTD
  • C/EBP
  • Estrogen receptor
  • HDL
  • LDL
  • PARP
  • PGC1α
  • PPARα
  • PPARγ
  • SREBP
  • atherosclerosis
  • cholesterol
  • lipophagy
  • lipotoxicity
  • nuclear receptor
  • polyunsaturated fatty acid
  • triglyceride

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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