02293nas a2200337   4500000000100000008004100001260001200042653001100054653001600065653001600081653003100097100001500128700001400143700001100157700001600168700001500184700001000199700001600209700001200225700001500237700001300252700001300265700001500278700001300293245014100306856007800447300001300525490000700538520139600545022001401941       2021                            d  c01/202110aLipids10aMacrophages10aCholesterol10aChromatography, Thin Layer1 aTanigawa K1 aHayashi Y1 aHama K1 aYamashita A1 aYokoyama K1 aLuo Y1 aKawashima A1 aMaeda Y1 aNakamura Y1 aHarada A1 aKiriya M1 aKarasawa K1 aSuzuki K00aMycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells.  uhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249184  ae02491840 v163 a<p>Mycobacterium leprae (M. leprae) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M. leprae. Lipids are an important nutrient for the intracellular survival of M. leprae. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M. leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M. leprae infection. We then used [14C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M. leprae. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M. leprae-infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells (GPAT3 KO) dramatically reduced accumulation of TAG following M. leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M. leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli.</p>  a1932-6203