PMID- 27662822
OWN - NLM
STAT- MEDLINE
DCOM- 20170717
LR  - 20181202
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 24
IP  - 11
DP  - 2016 Nov
TI  - The anti-adipogenic effect of peripheral blood mononuclear cells is absent with 
      PCSK9 loss-of-function variants.
PG  - 2384-2391
LID - 10.1002/oby.21656 [doi]
AB  - OBJECTIVE: 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. METHODS: 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. RESULTS: 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-1beta, tumor necrosis factor-alpha, 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. CONCLUSIONS: 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.
CI  - (c) 2016 The Obesity Society.
FAU - Gagnon, AnneMarie
AU  - Gagnon A
AD  - Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Ooi, Teik C
AU  - Ooi TC
AD  - Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Cousins, Marion
AU  - Cousins M
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Favreau, Colette
AU  - Favreau C
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Henry, Kathy
AU  - Henry K
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Landry, Anne
AU  - Landry A
AD  - Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
FAU - Sorisky, Alexander
AU  - Sorisky A
AD  - Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada. asorisky@ohri.ca.
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada. asorisky@ohri.ca.
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. 
      asorisky@ohri.ca.
LA  - eng
PT  - Journal Article
DEP - 20160924
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (CCL2 protein, human)
RN  - 0 (CD36 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
SB  - IM
MH  - Adipogenesis/*genetics
MH  - Aged
MH  - CD36 Antigens/metabolism
MH  - Case-Control Studies
MH  - Chemokine CCL2/metabolism
MH  - Culture Media, Conditioned
MH  - Fasting/metabolism
MH  - Female
MH  - *Genetic Variation
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Postprandial Period/genetics
MH  - Proprotein Convertase 9/*genetics
MH  - RNA, Messenger/metabolism
MH  - Sterol Regulatory Element Binding Protein 1/metabolism
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2016/11/03 06:00
MHDA- 2017/07/18 06:00
CRDT- 2016/09/25 06:00
PHST- 2016/06/15 00:00 [received]
PHST- 2016/07/26 00:00 [revised]
PHST- 2016/08/04 00:00 [accepted]
PHST- 2016/11/03 06:00 [pubmed]
PHST- 2017/07/18 06:00 [medline]
PHST- 2016/09/25 06:00 [entrez]
AID - 10.1002/oby.21656 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2016 Nov;24(11):2384-2391. doi: 10.1002/oby.21656. Epub 
      2016 Sep 24.