Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Adaption of skeletal muscle to endurance exercise includes PPARδ- and AMP-activated protein kinase (AMPK)/PPARγ coactivator 1α-mediated transcriptional responses that result in increased oxidative capacity and conversion of glycolytic to more oxidative fiber types. These changes are associated with whole-body metabolic alterations including improved glucose handling and resistance to obesity. Increased DHA (22:6n-3) content in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is also reported in endurance exercise-trained glycolytic muscle; however, the DHA-metabolizing enzymes involved and the biological significance of the enhanced DHA content are unknown. In the present study, we identified lysophosphatidic acid acyltransferase (LPAAT)3 as an enzyme that was upregulated in myoblasts during in vitro differentiation and selectively incorporated DHA into PC and PE. LPAAT3 expression was increased by pharmacological activators of PPARδ or AMPK, and combination treatment led to further increased LPAAT3 expression and enhanced incorporation of DHA into PC and PE. Our results indicate that LPAAT3 was upregulated by exercise-induced signaling pathways and suggest that LPAAT3 may also contribute to the enhanced phospholipid-DHA content of endurance-trained muscles. Identification of DHA-metabolizing enzymes in the skeletal muscle will help to elucidate broad metabolic effects of DHA.

DOI： 10.1194/jlr.m077321

PubMed

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/1873-3468.12825

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/1873-3468.12825

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietary DHA on visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA's effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knock-out mice. Dynamic light-scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics of DHA reduced membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knock-out mice exhibited abnormalities in the retinal layers, such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layers and impaired visual function, as well as disordered disc morphology in photoreceptor cells. Our results indicate that PL-DHA contributes to visual function by maintaining the disc shape in photoreceptor cells and that this is a function of DHA in the retina. This study thus provides the reason why DHA is required for visual acuity and may help inform approaches for overcoming retinal disorders associated with DHA deficiency or dysfunction.

DOI： 10.1074/jbc.m117.790568

PubMed

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Docosahexaenoic acid (DHA) is one of the essential ω-3 polyunsaturated fatty acids with a wide range of physiological roles important for human health. For example, DHA renders cell membranes more flexible and is therefore important for cellular function, but information on the mechanisms that control DHA levels in membranes is limited. Specifically, it is unclear which factors determine DHA incorporation into cell membranes and how DHA exerts biological effects. We found that lysophosphatidic acid acyltransferase 3 (LPAAT3) is required for producing DHA-containing phospholipids in various tissues, such as the testes and retina. In this study, we report that LPAAT3-KO mice display severe male infertility with abnormal sperm morphology. During germ cell differentiation, the expression of LPAAT3 was induced, and germ cells obtained more DHA-containing phospholipids. Loss of LPAAT3 caused drastic reduction of DHA-containing phospholipids in spermatids that led to excess cytoplasm around its head, which is normally removed by surrounding Sertoli cells via endocytosis at the final stage of spermatogenesis. In vitro liposome filtration assay raised the possibility that DHA in phospholipids promotes membrane deformation that is required for the rapid endocytosis. These data suggest that decreased membrane flexibility in LPAAT3-KO sperm impaired the efficient removal of sperm content through endocytosis. We conclude that LPAAT3-mediated enrichment of cell membranes with DHA-containing phospholipids endows these membranes with physicochemical properties needed for normal cellular processes, as exemplified by spermatogenesis.

DOI： 10.1074/jbc.m117.791277

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：eLife Sciences Publications, Ltd  

Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes.

DOI： 10.7554/elife.06328

PubMed

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Other Link： https://cdn.elifesciences.org/articles/06328/elife-06328-v2.pdf

Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

Glycerophospholipids are the main components of cellular membranes. Saturated (also monounsaturated) fatty acids and polyunsaturated fatty acids are usually esterified at the sn -1 and sn -2 position, respectively, in an asymmetrical manner. Using acyl-CoAs as donors, fatty acids of glycerophospholipids are regulated by lysophospholipid acyltransferases in a de novo pathway (Kennedy pathway) and a remodeling pathway (Lands’ cycle) to generate membrane diversity. Both pathways were reported in the 1950s. Fourteen lysophospholipid acyltransferases in the 1-acylglycerol-3-phosphate O -acyltransferase (AGPAT) and membranebound O -acyltransferases(MBOAT) families have been identified to date. In this section, recent studies reporting the cloning and characterization of mammalian lysophospholipid acyltransferases are summarized.

DOI： 10.1007/978-4-431-55669-5_1

Scopus

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cmet.2014.05.019

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1194/jlr.r046094

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1096/fj.13-237941

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.13-237941

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/jb/mvt048

CiNii Books

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1194/jlr.m800468-jlr200

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1194/jlr.r800035-jlr200

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Publishing type：Research paper (scientific journal)   Publisher：The American Association of Immunologists  

DOI： 10.4049/jimmunol.181.7.5008

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Proceedings of the National Academy of Sciences  

DOI： 10.1073/pnas.0712245105

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1074/jbc.m609641200

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bbrc.2007.01.028

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Adipose tissue plays a central role in energy homeostasis. In a previous report, we reported adipogenin, an adipocyte-specific membrane protein whose expression is higher in fat and increases during the adipocyte differentiation of 3T3-L1 cells, as a candidate gene for involvement in adipogenesis. Here, we isolated the bovine adipogenin gene using in silico cloning and the target region for polymerase chain reaction amplification in the database. cDNA, including a 246 base pair (bp) open reading frame, was identified in the adipose tissues of cattle. In silico gene analysis showed that the bovine adipo-genin-encoded protein has a predicted MW of 9882.45, encoding 81 amino acids and located on bovine chromosome 13. The deduced amino acid sequence of bovine adipogenin conserved 86%, 66% and 78% identity with that in pigs, mice and humans, respectively. A semi-quantitative reverse transcriptase polymerase chain reaction showed that bovine adipogenin mRNA was more highly expressed in subcutaneous, perirenal and mescentric adipose tissue than in non-adipose tissue. The level of bovine adipogenin mRNA is dramatically elevated during the adipocyte differentiation of four different kinds of preadipocytes prepared from subcutaneous, perirenal, mesenteric and parametrial adipose tissues. Our results suggest that adipogenin plays an important role in the regulation of adipocyte development in cattle and may be a strong candidate gene for obesity in mammals.

DOI： 10.1111/j.1740-0929.2006.00393.x

Web of Science

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1074/jbc.m600225200

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Publishing type：Research paper (scientific journal)   Publisher：The Endocrine Society  

It has recently been discovered that G protein-coupled receptors (GPCR) 41 and 43 are characterized by having the short chain fatty acids acetate and propionate as their ligands. The objective of this study was to investigate the involvement of GPCR41, GPCR43, and their ligands in the process of adipogenesis. We measured the levels of GPCR41 and GPCR43 mRNA in both adipose and other tissues of the mouse. GRP43 mRNA expression was higher in four types of adipose tissue than in other tissues, whereas GPCR41 mRNA was not detected in any adipose tissues. A high level of GPCR43 expression was found in isolated adipocytes, but expression level was very low in stromal-vascular cells. Expression of GPCR43 was up-regulated in adipose tissues of mice fed a high-fat diet compared with those fed a normal-fat diet. GPCR43 mRNA could not be detected in confluent and undifferentiated 3T3-L1 adipocytes; however, the levels rose with time after the initiation of differentiation. GPCR41 expression was not detected in confluent and differentiated adipocytes. Acetate and propionate treatments increased lipids present as multiple droplets in 3T3-L1 adipocytes. Propionate significantly elevated the level of GPCR43 expression during adipose differentiation, with up-regulation of PPAR-γ2. Small interfering RNA mediated a reduction of GPCR43 mRNA in 3T3-L1 cells and blocked the process of adipocyte differentiation. In addition, both acetate and propionate inhibited isoproterenol-induced lipolysis in a dose-dependent manner. We conclude that acetate and propionate short chain fatty acids may have important physiological roles in adipogenesis through GPCR43, but not through GPCR41.

DOI： 10.1210/en.2005-0545

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s11010-005-3673-0

CiNii Books

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Other Link： http://link.springer.com/article/10.1007/s11010-005-3673-0/fulltext.html

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：American Physiological Society  

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species.

DOI： 10.1152/physiolgenomics.00184.2004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

To investigate the role of claudin-6 in adipogenesis, claudin-6 mRNA was examined in adipose tissues and adipocyte differentiation. Claudin-6 mRNA was found to be differentially expressed in four different adipose tissues, and up-regulated in each fat depot of mice fed a high-fat diet as compared to a normal-fat diet. Levels of claudin-6 transcripts were increased during differentiation of 3T3-L1 cells in vitro. Moreover, small interfering RNA (siRNA)-mediated reduction of claudin-6 mRNA inhibited differentiation of 3T3-L1 cells. These results suggest that claudin-6 is another important regulator in adipogenesis and fat deposition.

DOI： 10.1271/bbb.69.2117

CiNii Books

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Publishing type：Research paper (scientific journal)   Publisher：The Endocrine Society  

DOI： 10.1210/en.2002-220783

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Visceral adipocytes differ in various biochemical properties from adipocytes of subcutaneous origin. However, information on differences in gene expression between visceral and subcutaneous fat depots is limited. Expression of the genes for the nonmuscle and muscle isoforms of the actin-binding protein cofilin was examined in subcutaneous and visceral fat depots of mice, pigs, and cattle by semiquantative reverse transcription and polymerase chain reaction analysis. The abundance of nonmuscle-type cofilin mRNA was markedly higher in visceral adipose tissue than in subcutaneous adipose tissue of mouse and pig. This difference was more pronounced in mice fed a high-fat diet than in those fed a standard diet. In cattle, however, the amount of nonmuscle-type cofilin mRNA was greater in subcutaneous fat than in visceral fat. Muscle-type cofilin mRNA was not detected in either adipose tissue of any of the three species. These results suggest that the nonmuscle isoform of cofilin, and therefore the cytoskeleton, may play a role in lipid accumulation in visceral adipose tissue.

DOI： 10.1271/bbb.67.2262

CiNii Books

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Language：Japanese  

CiNii Books

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