Acyl-CoA:glycerol-3-phosphate acyltransferase (GPAT) and acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT) are involved in the de novo synthesis of triacylglycerol (TAG) and glycerophospholipids. Many enzymes belonging to the GPAT/AGPAT family have recently been identified and their physiological or pathophysiological roles have been proposed. The roles of GPAT/AGPAT in the synthesis of TAG and obesity-related diseases were revealed through the identification of causative genes of these diseases or analyses of genetically manipulated animals. Recent studies have suggested that some isoforms of GPAT/AGPAT family enzymes are involved in the fatty acid remodeling of phospholipids. The enzymology of GPAT/AGPAT and their physiological/ pathological roles in the metabolism of glycerolipids have been described and discussed in this review.

The coenzyme A (CoA)-independent transacylation system catalyzes fatty acid transfer from phospholipids to lysophospholipids in the absence of cofactors such as CoA. It prefers to use C20 and C22 polyunsaturated fatty acids such as arachidonic acid, which are esterified in the glycerophospholipid at the sn-2 position. This system can also acylate alkyl ether-linked lysophospholipids, is involved in the enrichment of arachidonic acid in alkyl ether-linked glycerophospholipids, and is critical for the metabolism of eicosanoids and platelet-activating factor. Despite their importance, the enzymes responsible for these reactions have yet to be identified. In this review, we describe the features of the Ca²⁺-independent, membrane-bound CoA-independent transacylation system and its selectivity for arachidonic acid. We also speculate on the involvement of phospholipase A2 in the CoA-independent transacylation reaction.

We previously reported that lysophosphatidylinositol (LPI) functions as an endogenous agonist of GPR55, a novel cannabinoid receptor. However, the physiological roles of LPI-GPR55 have not yet been elucidated in detail. In the present study, we found that LPI induced morphological changes in GPR55-expressing HEK293 cells. LPI induced the cell rounding of GPR55-expressing HEK293 cells but not of empty-vector-transfected cells. LPI also induced the activation of small GTP-binding protein RhoA and increased stress fiber formation in GPR55-expressing HEK293 cells. The inhibition of RhoA and Rho kinase ROCK by the C3 exoenzyme and the ROCK inhibitor reduced LPI-induced cell rounding and stress fiber formation. These results clearly indicated that the LPI-induced morphological changes and the assembly of the cytoskeletons were mediated through the GPR55-RhoA-ROCK pathway.

Galectins are a family of β-galactoside-binding lectins. They are involved in the regulation of a variety of biological phenomena in mammals. However, little is known about their roles in invertebrates. Caenorhabditis elegans is a well-characterized model organism whose complete genome has been sequenced. C. elegans is now being studied extensively in various fields of medical sciences. In this study, we examined the phenotypes of a mutant strain of C. elegans (tm1262) lacking lec-10, a galectin-encoding gene. We observed no difference in the rates of embryonic lethality and larval arrest/slow growth between this mutant strain and the wild-type strain. No apparent morphological defect was observed in the lec-10-deletion mutant (tm1262). Moreover, the life-spans of this mutant and the wild-type strain were equivalent. However, this mutant showed significantly greater susceptibility to paraquat and hydrogen peroxide than the wild type did. The lec-10-deletion mutants (tm1262) were as susceptible as the daf-16-deletion mutants (mu86) to paraquat and hydrogen peroxide. These results suggest that the deletion of lec-10 does not have a notable effect on the worm's survival under laboratory conditions. However, this study indicates that lec-10 does confer some protection against oxidative stress.

LEC-1 is a major galectin in Caenorhabditis elegans and contains two carbohydrate recognition domains (CRDs), N-CRD and C-CRD. To determine the role of LEC-1, we examined the phenotypes of a mutant C. elegans strain lacking lec-1. We observed negligible differences in embryogenesis, morphogenesis and egg laying at 20°C between the mutant and the wild-type. Furthermore, the life spans of the mutant and the wild-type were equivalent at either 20°C or 25°C. However, the lec-1 mutant showed a greater susceptibility to H₂O₂ and paraquat than the wild-type. This result suggests an increased susceptibility to oxidative stress, with the phenotypes being similar to those of lec-10 deletion mutants as previously described. To understand the molecular mechanism underlying this phenotype, C. elegans proteins bound by either the LEC-1 N-CRD or C-CRD were isolated and identified using a nano liquid chromatography–tandem mass spectrometry technique. MIG-6 was identified as a major binding partner of LEC-1 with both N- and C-CRD. From these results and previous reports, we speculate that interaction of LEC-1 and MIG-6 in the pharynx may affect susceptibility to paraquat and that LEC-10 has different functions from LEC-1 in regulating H₂O₂ and paraquat resistance in the intestine.