Links between enhanced fatty acid flux, protein kinase C and NFκB activation, and apoB–lipoprotein production in the fructose-fed hamster model of insulin resistance

Ragheb, Rafik; Medhat, Amina M.; Shanab, Gamila M. L.; Seoudi, Dina M.; Fantus, I. George

doi:10.1016/j.bbrc.2008.03.044

Cited by 20 publications

(23 citation statements)

References 27 publications

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“…However, we did not determine which isoform of PKC is involved in the regulation. It was reported that enhanced fatty acid flux increases the activation of the PKC isoforms, PKC␣/␤II, and of NFB (20). Therefore, PKC␣/␤II might be involved in PKC activation induced by ATGL knockdown; however, further studies are necessary.…”

Section: Discussionmentioning

confidence: 97%

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Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

Inoue

Kobayashi

Inoguchi

et al. 2011

Journal of Biological Chemistry

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Background: Adipose triglyceride lipase (ATGL) expression is decreased in the obese insulin-resistant state. Results: RNA interference-mediated down-regulation of ATGL enhanced monocyte adhesion via increased expression of tumor necrosis factor ␣-induced intercellular adhesion molecule-1. Conclusion: Reduced ATGL expression may influence the atherogenic process in the insulin-resistant state. Significance: This mechanism also leads to the acceleration of atherosclerosis in patients with insulin-resistance, even if not in a state of hyperglycemia.

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Section: Discussionmentioning

confidence: 97%

“…Effect of ATGL Knockdown on Diacylglycerol MetabolismFree fatty acids activate PKC via increased synthesis of DAG, a potent activator of PKC (19,20). We next examined the effect of ATGL knockdown on DAG levels and found that total DAG levels were increased 1.3-fold in ATGL knockdown HAECs (Fig.…”

Section: Atgl Knockdown Haecsmentioning

confidence: 97%

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

Inoue

Kobayashi

Inoguchi

et al. 2011

Journal of Biological Chemistry

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“…After phosphorylation, IjB is ubiquitinated and degraded in the proteaosome, releasing nuclear factor jB (NF-jB) for the translocation to the nucleus and activation of gene expression (Cai et al 2004). It has been proposed that increased NF-jB activation may play an important role in the pathogenesis of insulin resistance (Ragheb et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats

et al. 2011

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Obesity-induced endoplasmatic reticulum (ER) stress has been demonstrated to underlie the induction of obesity-induced JNK and NF-κB activation inflammatory responses, and generation of peripheral insulin resistance. On the other hand, exercise has been used as a crucial tool in obese and diabetic patients, and may reduce inflammatory pathway stimulation. However, the ability of exercise training to reverse endoplasmatic reticulum stress in adipose and hepatic tissue in obesity has not been investigated in the literature. Here, we demonstrate that exercise training ameliorates ER stress and insulin resistance in DIO-induced rats. Rats were fed with standard rodent chow (3,948 kcal kg(-1)) or high-fat diet (5,358 kcal kg(-1)) for 2 months. After that rats were submitted to swimming training (1 h per day, 5 days for week with 5% overload of the body weight for 8 weeks). Samples from epididymal fat and liver were obtained and western blot analysis was performed. Our results showed that swimming protocol reduces pro-inflammatory molecules (JNK, IκB and NF-κB) in adipose and hepatic tissues. In addition, exercise leads to reduction in ER stress, by reducing PERK and eIF2α phosphorylation in these tissues. In parallel, an increase in insulin pathway signaling was observed, as confirmed by increases in IR, IRSs and Akt phosphorylation following exercise training in DIO rats. Thus, results suggest that exercise can reduce ER stress, improving insulin resistance in adipose and hepatic tissue.

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“…Whether this scenario participates in high FFAinduced inhibition of PLC-activating agonist effects on [Ca 2C ] i and eNOS remains to be investigated. An elevation of FFA concentrations is also able to activate PKC (Griffin et al 1999, Inoguchi et al 2000, Rask-Madsen & King 2007, Ragheb et al 2008, which may cause inhibition of endothelium-dependent vascular relaxation in vascular rings (Davda et al 1994). Our results using PKC inhibitors suggested that excessive PKC activation is a candidate mechanism for the alterations of NO production, [Ca 2C ] i elevation, and eNOS activity in response to agonists in ECs chronically exposed to FFA overload.…”

Section: Cmentioning

confidence: 65%

Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+ levels in endothelial cells

Tang¹,

Li²

2011

Journal of Molecular Endocrinology

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Dyslipidemia is a common metabolic disorder in diabetes. Nitric oxide (NO) production from endothelium plays the primary role in endothelium-mediated vascular relaxation and other endothelial functions. Therefore, we investigated the effects of elevated free fatty acids (FFA) on the stimulation of NO production by phospholipase C (PLC)-activating receptor agonists (potent physiological endothelium-dependent vasodilators) and defined the possible alterations of signaling pathways implicated in this scenario. Exposure of bovine aortic endothelial cells (BAECs) to high concentrations of a mixture of fatty acids (oleate and palmitate) for 5 or 10 days significantly reduced NO production evoked by receptor agonists (bradykinin or ATP) in a time-and dose-dependent manner. Such defects were not associated with alterations of either endothelial NO synthase mass or inositol phospholipid contents but were probably due to reduced elevations of intracellular free Ca 2C levels ([Ca 2C ] i ) under these conditions. Exposure of BAECs to FFA significantly attenuated agonist-induced [Ca 2C ] i increases by up to 54% in a dose-and time-dependent manner. Moreover, bradykinin receptor affinity on the cell surface was significantly decreased by high concentrations of FFA. The morphology of BAECs was altered after 10-day culture with high FFA. Co-culture with protein kinase C (PKC) inhibitors or antioxidants was able to reverse the impairments of receptor agonist-induced NO production and [Ca 2C ] i rises as well as the alteration of receptor affinity in BAECs exposed to FFA. These data indicate that chronic exposure to high FFA reduces NO generation in endothelial cells probably by impairing PLC-mediated Ca 2C signaling pathway through activation of PKC and excess generation of oxidants.

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Links between enhanced fatty acid flux, protein kinase C and NFκB activation, and apoB–lipoprotein production in the fructose-fed hamster model of insulin resistance

Cited by 20 publications

References 27 publications

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats

Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+ levels in endothelial cells

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