Coordinate induction of genes involved in chylomicron synthesis and clearance is delayed in MetS mice.

<p>After overnight fasting, control and MetS mice were gavaged with 0.5 mL oil and sacrificed 1 and 6 h later. Jejunal mRNA levels of genes of interest were evaluated by real-time PCR and normalized to 36B4 mRNA. Induction of gene expression is shown at 1 h (A) and 6 h (B) after the lipid load as compared with fasting in control and MetS mice. Means ± SEM, n = 5 or 6, *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001. Induction of gene expression obtained from control and MetS mice was also compared across groups # <i>P</i> < 0.05, ## <i>P</i> < 0.01.</p

Lipid-mediated induction of genes involved in chylomicron synthesis is dependent on CD36 proteasomal degradation.

<p>Fasted CD36 (+/+) and CD36 (-/-) mice were intraperitoneally injected with MG132 (14 mg/kg) 30 min before oil gavage and sacrificed 4 h later. (A) CD36 expression standardized to HSC70 as the loading control. (B) mRNA level analysis by real-time PCR normalized to 36B4 mRNA. Means ± SEM, n = 5. *<i>P</i> < 0.05.</p

MetS mice display higher postprandial lipemia than controls and altered TRL particle distribution.

<p>Plasma TG (A) and NEFA (B) quantified after an intragastric lipid load (0.5 mL) in control and MetS mice. TG secretion as a function of time after or not the lipid load in mice pre-injected retro-orbitally with the LPL inhibitor (tyloxapol, 500 mg/kg) (C). Lipoprotein particle distribution in the plasma estimated using DLS in mice injected with tyloxapol at 1h (D), 2 h (E) and 4 h (F) after the lipid bolus. Means ± SEM, n = 8 (A, B and C), n = 5 (D, E), n = 11 (F), means with same letter are not significantly different, *<i>P</i> < 0.05, ***<i>P</i> < 0.001.</p

Streptozotocin treatment restores lipid-downregulation of CD36 and its associated effects in MetS mice.

<p>A retro-orbital injection of streptozotocin (100 mg/kg) was performed in fasted MetS mice. Six days later, fasted MetS mice were treated with tyloxapol (500mg/kg), given a lipid-bolus and sacrificed 1.5 h later. (A) CD36 expression in jejunal mucosa (B) Streptozotocin effect on mRNA levels of key chylomicron genes by real-time PCR with data normalized to 36B4 mRNA (C). Plasma TG secretion. Means ± SEM, n = 5, *P<0.05.</p

Small intestinal effects of postprandial hyperinsulinemia in MetS mice.

<p>Plasma insulin levels at 0 (fasted) and 1 and 6 h after the lipid load. Means with same letter are not significantly different (A). AKT activation in the jejunal mucosa from overnight fasted control and MetS mice 1 h after the lipid bolus. Phosphorylated AKT level was standardized to total AKT (B). mRNA levels of the insulin receptor and insulin receptor substrate 1 in fasted mice measured by real-time PCR (normalized to 36B4 mRNA). Means ± SEM, n = 5 or 6, * <i>P</i> < 0.05 (C). Correlation between plasma insulin level and percentage drop in jejunal CD36 protein in control and MetS mice, 1 and 6 h after a lipid load expressed relative to levels in fasted mice. Pearson correlation, n = 22, P<0.05 (D).</p

Genes involved in chylomicron synthesis are upregulated by fatty acids in ileum of MetS mice.

<p>After an overnight fast, control and MetS mice were gavaged with 0.5 mL oil and sacrificed 6 h later. Ileal gene expression levels were evaluated by real-time PCR and normalized to 36B4 mRNA. Data presented show induction of gene expression 6 h after the lipid load as compared with fasting in control and MetS mice. Means ± SEM, n = 5 or 6, *<i>P</i> < 0.05.</p