Figures & data
Figure 2 Mechanism of action of the PAF via platelet activation to induce NAFLD. The binding of the PAF to the PAFR will induce platelet activation and stimulate the secretion of 5-HT, IP3, AA and DAG by platelets or multiple cells. IP3, by regulating Ca2+ mobilisation, may trigger endoplasmic reticulum stress (ERS). AA can be further converted to LTs, PG and TXA2. PG mainly includes PGI2, PGE2, PGD2 and PGF2α. The activation of DAG induces the activation of p38MAPK and PKC (PKCε and PKCδ), and PKCδ may agonise ERS. Moreover, 5-HT, AA and TXA2 further stimulate the PAF and amplify platelet activation. Subsequently, these substances induce cascade reactions that may be involved in NAFLD development by promoting the development of oxidative stress, inflammatory responses or insulin resistance.
![Figure 2 Mechanism of action of the PAF via platelet activation to induce NAFLD. The binding of the PAF to the PAFR will induce platelet activation and stimulate the secretion of 5-HT, IP3, AA and DAG by platelets or multiple cells. IP3, by regulating Ca2+ mobilisation, may trigger endoplasmic reticulum stress (ERS). AA can be further converted to LTs, PG and TXA2. PG mainly includes PGI2, PGE2, PGD2 and PGF2α. The activation of DAG induces the activation of p38MAPK and PKC (PKCε and PKCδ), and PKCδ may agonise ERS. Moreover, 5-HT, AA and TXA2 further stimulate the PAF and amplify platelet activation. Subsequently, these substances induce cascade reactions that may be involved in NAFLD development by promoting the development of oxidative stress, inflammatory responses or insulin resistance.](/cms/asset/b1f98c2d-61d3-4bae-9423-6a4976b8082d/dmso_a_367483_f0002_c.jpg)
Figure 3 PAF activates 5-hydroxytryptamine to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates 5-HT release, which is involved in NAFLD development mainly by inducing oxidative stress, inflammatory response and insulin resistance.
![Figure 3 PAF activates 5-hydroxytryptamine to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates 5-HT release, which is involved in NAFLD development mainly by inducing oxidative stress, inflammatory response and insulin resistance.](/cms/asset/3afc81f5-45f6-4787-ac02-0bdcc1348924/dmso_a_367483_f0003_c.jpg)
Figure 4 PAF activates inositol triphosphate to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces IP3 production, and IP3 binding to the IP3R promotes Ca2+ release, damages mitochondria and induces IR. Moreover, Ca2+ overload may induce ER stress. ER stress is associated with the development of oxidative stress, inflammatory responses and insulin resistance, which contribute to NAFLD development.
![Figure 4 PAF activates inositol triphosphate to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces IP3 production, and IP3 binding to the IP3R promotes Ca2+ release, damages mitochondria and induces IR. Moreover, Ca2+ overload may induce ER stress. ER stress is associated with the development of oxidative stress, inflammatory responses and insulin resistance, which contribute to NAFLD development.](/cms/asset/d3799016-9a93-43e4-bdeb-a48724055ca8/dmso_a_367483_f0004_c.jpg)
Figure 5 PAF activates AA to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates AA release, which is involved in NAFLD development mainly by inducing oxidative stress, inflammatory response and IR.
![Figure 5 PAF activates AA to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates AA release, which is involved in NAFLD development mainly by inducing oxidative stress, inflammatory response and IR.](/cms/asset/3dbff79e-2a60-4151-b940-4c6e945a8bfb/dmso_a_367483_f0005_c.jpg)
Figure 6 PAF activates the AA–LTs signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAF receptor stimulates the release of AA, which induces LTs release and is involved in NAFLD development mainly by inducing inflammatory responses and insulin resistance.
![Figure 6 PAF activates the AA–LTs signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAF receptor stimulates the release of AA, which induces LTs release and is involved in NAFLD development mainly by inducing inflammatory responses and insulin resistance.](/cms/asset/d7c86efb-90ac-422e-9136-1fc46234852a/dmso_a_367483_f0006_c.jpg)
Figure 7 PAF activates the AA–PG/TXA2 signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates AA release, which induces the synthesis of PG and TXA2; PG mainly included PGI2, PGE2, PGD2 and PGF2α. These substances are involved in NAFLD development mainly through the induction of oxidative stress, inflammatory response and insulin resistance.
![Figure 7 PAF activates the AA–PG/TXA2 signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR stimulates AA release, which induces the synthesis of PG and TXA2; PG mainly included PGI2, PGE2, PGD2 and PGF2α. These substances are involved in NAFLD development mainly through the induction of oxidative stress, inflammatory response and insulin resistance.](/cms/asset/96f54bac-ff4a-41c2-b9d7-74cb3fb9b7ce/dmso_a_367483_f0007_c.jpg)
Figure 8 PAF activates the DAG–PKCε/PKCδ signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces DAG production. The activation of DAG induces PKC (PKCε and PKCδ) activation, and PKCδ may also agonise endoplasmic reticulum stress. This pathway is involved in NAFLD development mainly through the induction of oxidative stress, inflammatory response and insulin resistance.
![Figure 8 PAF activates the DAG–PKCε/PKCδ signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces DAG production. The activation of DAG induces PKC (PKCε and PKCδ) activation, and PKCδ may also agonise endoplasmic reticulum stress. This pathway is involved in NAFLD development mainly through the induction of oxidative stress, inflammatory response and insulin resistance.](/cms/asset/5c24f08a-5940-4c0f-bf7e-3873b5bea365/dmso_a_367483_f0008_c.jpg)
Figure 9 PAF activates DAG–p38MAPK signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces DAG production. The activation of DAG induces p38MAPK activation, which is involved in NAFLD development by inducing inflammatory responses and IR.
![Figure 9 PAF activates DAG–p38MAPK signalling pathway to promote the mechanism of NAFLD development. The binding of PAF to PAFR induces DAG production. The activation of DAG induces p38MAPK activation, which is involved in NAFLD development by inducing inflammatory responses and IR.](/cms/asset/0e5fe555-0e13-479f-9a9d-7e1e4fb5967e/dmso_a_367483_f0009_c.jpg)