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S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

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S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9. Hepatic apoCIII mRNA is repressed in LIR-KO mice - PowerPoint PPT Presentation

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Page 1: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Page 2: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Hepatic apoCIII mRNA is repressed

in LIR-KO mice

Expression of apoCIII (A) and LPK (B) mRNA levels were measured by real-time quantitative polymerase chain reaction in livers of nonfasted (NF), fasted for 24 hours (F) and refed with a high-carbohydrate diet (RF) wild-type (white) and LIR-KO (black)

mice. *P<0.05.

S. Caron, et al. ATVB 2011;31:513-9

Page 3: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Glucose induces apoCIII expression and promoter

activity in primary rat hepatocytes

A, ApoCIII protein secretion into the supernatant of primary rat hepatocytes after 24 hours of incubation in medium containing a low (open bars) or high (solids bars) glucose concentration. B, Kinetics of apoCIII mRNA in primary rat hepatocytes during 24 hours of incubation in medium containing a low (open circles) or high (solid squares) glucose concentration. C, Dose dependence of apoCIII mRNA in primary rat hepatocytes after 24 hours of incubation in medium containing the indicated concentrations of glucose. D, ApoCIII mRNA in primary rat hepatocytes pretreated with actinomycin D and subsequently incubated in medium containing a low (open bars) or high (solid bars) glucose concentration for 24 hours. E, Activity of the human apoCIII promoter (-1200/+24) in transfected primary rat hepatocytes after 24 hours of incubation in medium containing a low (open bars) or high (solid bars) glucose concentration. F, Activity of the wild-type or mutated C3P footprint in transfected primary rat hepatocytes after 24 hours of incubation in medium containing a low (open bars) or high (solid bars) glucose concentration.

S. Caron, et al. ATVB 2011;31:513-9

Page 4: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Glucose induces apoCIII expression and promoter activity in IHH

S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Page 5: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Glucose induction of apoCIII mRNA expression in IHH involves the transcription factors HNF-4α and ChREBP

S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Page 6: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Activation of the nuclear receptors FXR and PPARα,

but not LXRs, inhibits apoCIII mRNA induction by

glucose in IHHActivation of the nuclear receptors FXR and PPARα, but not LXRs, inhibits apoCIII mRNA induction by glucose in IHH. Effects of FXR (5 µmol/L GW4064) (A), PPAR α (100 µmol/L ciprofibrate [CF]) (B), and LXRs (1 µmol/L T0901317) (C) activation on apoCIII mRNA expression in IHH after 24 hours of incubation in medium containing low (open bars) or high (solid bars) glucose concentration. mRNA expression levels were measured by real-time quantitative polymerase chain reaction.

S. Caron, et al. ATVB 2011;31:513-9

Page 7: S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9

Correlation of Plasma ApoCIII Protein Levels With Metabolic Parameters of Glucose

Homeostasis in Drug-Naïve Overweight Patients

S. Caron, et al. Arterioscler Thromb Vasc Biol 2011;31:513-9