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. Author manuscript; available in PMC: 2016 Aug 1.
Published in final edited form as: Metabolism. 2016 Mar 3;65(8):1049–1061. doi: 10.1016/j.metabol.2016.02.014

Table1.

Lipid types and mechanisms of liver injury.

Lipid Types Pathways mediating hepatic injury References
Free Fatty Acids
(FFA)/
Lysophosphatidyl
choline (LPC)
  • –

    Activate PPARα resulting in impairment of insulin signaling

 Ricchi, 2009
  • –

    Phosphorylate and activate JNK which upregulates PUMA leading to Bax activation, mitochondrial dysfunction, caspases activation and apoptosis

  • –

    Upregulate of DR5 in JNK-dependent manner and sensitize hepatocytes to TRAIL-induced apoptosis

  • –

    Activate an ER stress and induce the expression of pro-apoptotic transcription factor CHOP which upregulates BIM and DR5

 Cazanave,
2009; Malhi,
2006;
Pagliassotti,
2007

Malhi, 2007


Cazanave, 2011
  • –

    Induce p62-dependent degradation of Keap1, leading to upregulation of BIM and PUMA

 Lee, 2012; Lin,
2013; Cazanave,
2014
Triglycerides
(TG)
  • –

    Hydrolyzed into FFAs

  • –

    Represent a safe fat storage for hepatocytes

  • –

    Have a protective role against the pro-apoptotic effect of unsaturated FFA

 Ricchi, 2009;
Listenberger,
2003;
Yamaguchi,
2007
Ceramides
  • –

    Interact with TNFα with release of ROS

  • –

    Increase pro-inflammatory cytokines

 Pagadala, 2012;
Schwabe, 2006
Free Cholesterol
(FC)
  • –

    Stimulates Kupffer cells and hepatic stellate cells to mediate fibrosis, mitochondrial dysfunction, ROS, and UPR culminating in apoptosis

 Arguello, 2015;
Tomita, 2014
  • –

    induces mitochondrial dysfunctions and hepatocyte injury through accumulation of oxysterol, a toxic oxidative product of cholesterol

 Musso, 2013
  • –

    Activates HMGB1 through a JNK-1 mediated mechanism

 Gan, 2014
Bile Acids
  • –

    Trigger hepatic apoptosis through JNK1/p53/SIRT1 pathway

 Ferreira, 2014

c-Jun NH2 terminal kinase (JNK), p53 upregulated modulator of apoptosis (PUMA), death receptor 5 (DR5), TNFα related apoptosis inducing ligand (TRAIL), endoplasmic reticulum (ER), CAATT enhancer binding homologous protein (CHOP), Bcl-2 interacting mediator (BIM), Kelch like ECH associated protein 1 (Keap1), Reactive oxygen species (ROS), unfolded protein response (UPR), sirtuin 1 (SIRT1).