Platelet-activating factor (PAF) and
lysophosphatidylcholine (LPC) are potent inflammatory
lipids. Elevated levels of PAF and LPC are associated with the onset of
diabetic retinopathy and neurodegeneration. However, the molecular mechanisms underlying such defects remain elusive. LPCAT1 is a newly reported
lysophospholipid acyltransferase implicated in the anti-inflammatory response by its role in conversion of LPC to PC. Intriguingly, the LPCAT1
enzyme also catalyzes the synthesis of PAF from
lyso-PAF with use of
acetyl-CoA as a substrate. The present studies investigated regulatory roles of LPCAT1 in the synthesis of inflammatory
lipids during the onset of diabetes. Our work shows that LPCAT1 plays an important role in the inactivation of PAF by catalyzing the synthesis of alkyl-PC, an inactivated form of PAF with use of
acyl-CoA and
lyso-PAF as substrates. In support of a role of LPCAT1 in anti-inflammatory responses in
diabetic retinopathy, LPCAT1 is most abundantly expressed in the retina. Moreover, LPCAT1
mRNA levels and
acyltransferase activity toward
lyso-PAF and LPC were significantly downregulated in retina and brain tissues in response to the onset of diabetes in Ins2(Akita) and db/db mice, mouse models of type 1 and
type 2 diabetes, respectively. Conversely, treatment of db/db mice with
rosiglitazone, an antidiabetes compound, significantly upregulated LPCAT1
mRNA levels concurrently with increased
acyltransferase activity in the retina and brain. Collectively, these findings identified a novel regulatory role of LPCAT1 in catalyzing the inactivation of inflammatory
lipids in the retina of diabetic mice.