PubMed:27662822 JSONTXT

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anti-adipogenic effect of peripheral blood mononuclear cells is absent with PCSK9 loss-of-function variants.\nOBJECTIVE: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis.\nMETHODS: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load.\nRESULTS: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load. Conditioned medium from PBMC was obtained in fasting (PBMC-CM-F) and 4-h postprandial (PBMC-CM-PP) states. PBMC-CM-PP from non-variant controls inhibited adipogenesis of human preadipocytes more than did PBMC-CM-F. In contrast, PBMC-CM-F or -PP from PCSK9 LOF variant subjects had no effect on adipogenesis. After the oral fat load, PBMC from PCSK9 LOF variant subjects showed significant increases in mRNA levels of interleukin-1β, tumor necrosis factor-α, sterol regulatory element binding protein-1c, CD36, and monocyte chemoattractant protein-1 (MCP-1), only MCP-1 mRNA levels increased in PBMC from non-variant controls.\nCONCLUSIONS: The absence of anti-adipogenic action of PBMC from PCSK9 LOF variant subjects points to a novel role for PCSK9 in PBMC-adipose cell interactions."}

{"project":"kaiyin_test","denotations":[{"id":"T5","span":{"begin":4,"end":26},"obj":"MPA"},{"id":"T4","span":{"begin":68,"end":74},"obj":"NegReg"},{"id":"T1","span":{"begin":80,"end":85},"obj":"Gene"},{"id":"T3","span":{"begin":86,"end":102},"obj":"NegReg"},{"id":"T2","span":{"begin":103,"end":111},"obj":"Var"},{"id":"T7","span":{"begin":234,"end":250},"obj":"NegReg"},{"id":"T6","span":{"begin":257,"end":264},"obj":"Var"},{"id":"T8","span":{"begin":335,"end":342},"obj":"NegReg"},{"id":"T9","span":{"begin":343,"end":361},"obj":"MPA"},{"id":"T10","span":{"begin":917,"end":922},"obj":"Gene"},{"id":"T28","span":{"begin":923,"end":926},"obj":"NegReg"},{"id":"T12","span":{"begin":927,"end":934},"obj":"Var"},{"id":"T13","span":{"begin":961,"end":973},"obj":"MPA"},{"id":"T14","span":{"begin":1010,"end":1015},"obj":"Gene"},{"id":"T29","span":{"begin":1016,"end":1019},"obj":"NegReg"},{"id":"T15","span":{"begin":1020,"end":1027},"obj":"Var"},{"id":"T17","span":{"begin":1056,"end":1065},"obj":"PosReg"},{"id":"T18","span":{"begin":1069,"end":1098},"obj":"MPA"},{"id":"T19","span":{"begin":1100,"end":1123},"obj":"MPA"},{"id":"T20","span":{"begin":1125,"end":1169},"obj":"MPA"},{"id":"T21","span":{"begin":1171,"end":1175},"obj":"MPA"},{"id":"T22","span":{"begin":1310,"end":1317},"obj":"NegReg"},{"id":"T23","span":{"begin":1321,"end":1343},"obj":"MPA"},{"id":"T24","span":{"begin":1357,"end":1362},"obj":"Gene"},{"id":"T25","span":{"begin":1367,"end":1374},"obj":"Var"},{"id":"T27","span":{"begin":1396,"end":1406},"obj":"PosReg"},{"id":"T26","span":{"begin":1438,"end":1450},"obj":"Interaction"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R10","pred":"CauseOf","subj":"T25","obj":"T22"},{"id":"R11","pred":"CauseOf","subj":"T25","obj":"T27"},{"id":"R12","pred":"ThemeOf","subj":"T26","obj":"T27"},{"id":"R13","pred":"ThemeOf","subj":"T10","obj":"T12"},{"id":"R14","pred":"CauseOf","subj":"T12","obj":"T28"},{"id":"R15","pred":"ThemeOf","subj":"T13","obj":"T28"},{"id":"R16","pred":"ThemeOf","subj":"T14","obj":"T15"},{"id":"R17","pred":"CauseOf","subj":"T15","obj":"T29"},{"id":"R18","pred":"CauseOf","subj":"T15","obj":"T17"},{"id":"R19","pred":"ThemeOf","subj":"T18","obj":"T17"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T3"},{"id":"R20","pred":"ThemeOf","subj":"T19","obj":"T17"},{"id":"R21","pred":"ThemeOf","subj":"T20","obj":"T17"},{"id":"R22","pred":"ThemeOf","subj":"T21","obj":"T17"},{"id":"R3","pred":"CauseOf","subj":"T3","obj":"T4"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T4"},{"id":"R5","pred":"CauseOf","subj":"T6","obj":"T7"},{"id":"R6","pred":"CauseOf","subj":"T7","obj":"T8"},{"id":"R7","pred":"ThemeOf","subj":"T9","obj":"T8"},{"id":"R8","pred":"ThemeOf","subj":"T23","obj":"T22"},{"id":"R9","pred":"ThemeOf","subj":"T24","obj":"T25"}],"text":"The anti-adipogenic effect of peripheral blood mononuclear cells is absent with PCSK9 loss-of-function variants.\nOBJECTIVE: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis.\nMETHODS: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load.\nRESULTS: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load. Conditioned medium from PBMC was obtained in fasting (PBMC-CM-F) and 4-h postprandial (PBMC-CM-PP) states. PBMC-CM-PP from non-variant controls inhibited adipogenesis of human preadipocytes more than did PBMC-CM-F. In contrast, PBMC-CM-F or -PP from PCSK9 LOF variant subjects had no effect on adipogenesis. After the oral fat load, PBMC from PCSK9 LOF variant subjects showed significant increases in mRNA levels of interleukin-1β, tumor necrosis factor-α, sterol regulatory element binding protein-1c, CD36, and monocyte chemoattractant protein-1 (MCP-1), only MCP-1 mRNA levels increased in PBMC from non-variant controls.\nCONCLUSIONS: The absence of anti-adipogenic action of PBMC from PCSK9 LOF variant subjects points to a novel role for PCSK9 in PBMC-adipose cell interactions."}

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