The anti-adipogenic effect of peripheral blood mononuclear cells is absent with PCSK9 loss-of-function variants.
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.



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.



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.



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.
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
AnneMarie
A
Gagnon
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Teik C
TC
Ooi
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Marion
M
Cousins
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Colette
C
Favreau
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Kathy
K
Henry
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Anne
A
Landry
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. asorisky@ohri.ca.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. asorisky@ohri.ca.|Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. asorisky@ohri.ca.
Alexander
A
Sorisky
D050156:Adipogenesis / Q000235:genetics*; D000368:Aged; D018955:CD36 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D017077:Culture Media, Conditioned; D005215:Fasting / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000235:genetics; D000071449:Proprotein Convertase 9 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C111835:CCL2 protein, human; D018955:CD36 Antigens; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9