Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver.

@article{Boden2005FreeFA,
  title={Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver.},
  author={Guenther H. Boden and Pengxiang She and Maria Mozzoli and Peter Cheung and Kiranmai Gumireddy and P. J. Reddy and X. Xiang and Z Luo and Neil B. Ruderman},
  journal={Diabetes},
  year={2005},
  volume={54 12},
  pages={
          3458-65
        }
}
To study mechanisms by which free fatty acids (FFAs) cause hepatic insulin resistance, we have used euglycemic-hyperinsulinemic clamping with and without infusion of lipid/heparin (to raise or to lower plasma FFAs) in alert male rats. FFA-induced hepatic insulin resistance was associated with increased hepatic diacylglycerol content (+210%), increased activities of two serine/threonine kinases (protein kinase C-delta and inhibitor of kappaB [IkappaB] kinase-beta), increased activation of the… Expand
Free fatty acids induce endothelial dysfunction and activate protein kinase C and nuclear factor-κB pathway in rat aorta.
TLDR
The molecular mechanisms underlying F FA-induced endothelial insulin resistance and eNOS inhibition may provide an important link implicating the PKC and IκB-α/NF-κB pathways in FFA-mediated inhibition of vascular insulin signaling. Expand
Links between enhanced fatty acid flux, protein kinase C and NFkappaB activation, and apoB-lipoprotein production in the fructose-fed hamster model of insulin resistance.
TLDR
Evidence is shown that free fatty acid (FFA) can induce hepatic insulin resistance in part via PKC activation leading to increased production of atherogenic apoB100-containing lipoproteins, and the general PKC inhibitor, bisindolylmaleimide-I, Bis-I was found to ameliorate fructose-induced insulin resistance, restoring the phosphorylation status of PKB and suppressing apo B100 overproduction in ex vivo and in vivo. Expand
FFA-induced hepatic insulin resistance in vivo is mediated by PKCδ, NADPH oxidase, and oxidative stress.
TLDR
It is suggested that the pathway of FFA-induced hepatic insulin resistance is FFA → PKCδ → NADPH oxidase and oxidative stress → IKKβ/JNK → impaired insulin signaling. Expand
Taurine prevents free fatty acid-induced hepatic insulin resistance in association with inhibiting JNK1 activation and improving insulin signaling in vivo.
  • Na Wu, Y. Lu, +6 authors P. Han
  • Medicine
  • Diabetes research and clinical practice
  • 2010
TLDR
Taurine co-infusion with IH prevented the rise in 8-isoprostaglandin and MDA, inhibited the activation of JNK1, and improved insulin signaling and insulin resistance in liver, suggesting the therapeutic value of taurine in protecting from hepatic insulin resistance caused by elevated FFAs. Expand
NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance.
TLDR
It is reported that both non-esterified ('free') fatty acids and fetuin-A coexist at high levels in the serum of db/db mice, indicating an association between them and a new dimension of lipid-induced insulin resistance and open another contemporary target for therapeutic intervention in Type 2 diabetes. Expand
Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats
TLDR
Fructose-rich diet led to an enhancement of 11βHSD1 protein level in the liver, without affecting intracellular level of corticosterone and downstream glucocorticoid signaling, finally leading to disruption of insulin signaling in the rat liver. Expand
Roles of plasma interleukin-6 and tumor necrosis factor-alpha and FFA and TG in the development of insulin resistance induced by high-fat diet.
TLDR
The results indicate that the progression of insulin resistance in high-fat diet rats is closely related to the plasma FFA elevation and the heterotopic deposition of TG in liver and skeletal muscles, but is unrelated to the Plasma TNF-alpha and IL-6 levels. Expand
p 38 Mitogen-Activated Protein Kinase Mediates Palmitate-Induced Apoptosis But Not Inhibitor of Nuclear Factor-B Degradation in Human Coronary Artery Endothelial Cells
Plasma free fatty acids are elevated in patients with type 2 diabetes and contribute to the pathogenesis of insulin resistance and endothelial dysfunction. The p38 MAPK mediates stress, inflammation,Expand
In Vivo Effects of Insulin and Free Fatty Acids on Matrix Metalloproteinases in Rat Aorta
TLDR
FFA augmented insulin stimulation of the MMP/TIMP balance of three proatherogenic MMPs and increased activities of two MAPKs, both of which are known to stimulate the production of proinflammatory cytokines, which may, over time, increase degradation of extracellular matrix and together with inflammatory changes promote development of ASVD. Expand
Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver
  • G. Boden
  • Medicine
  • Current diabetes reports
  • 2006
TLDR
Elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which produces proinflammatory and proatherogenic cytokines, which contribute to theDevelopment of atherosclerotic vascular diseases and NAFLD. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
TLDR
It is shown that lipid accumulation in the liver leads to subacute hepatic 'inflammation' through NF-κB activation and downstream cytokine production, which causes insulin resistance both locally in liver and systemically. Expand
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle*
TLDR
The hypothesis that an increase in plasma fatty acid concentration results in a increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-θ leading to increased IRS-1 Ser307 phosphorylation is supported. Expand
Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.
TLDR
Data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity. Expand
Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α
TLDR
The results indicated that the insulin resistance observed in human muscle when plasma FFA levels were elevated during euglycemic-hyperinsulinemic clamping was associated with increases in DAG mass and membrane-associated PKC-betaII and -delta and a decrease in IkappaB-alpha. Expand
Mechanism of Hepatic Insulin Resistance in Non-alcoholic Fatty Liver Disease*
TLDR
The hypothesis hepatic steatosis leads to hepatic insulin resistance by stimulating gluconeogenesis and activating PKC-ϵ and JNK1, which may interfere with tyrosine phosphorylation of IRS-1 and IRS-2 and impair the ability of insulin to activate glycogen synthase is supported. Expand
Free fatty acids as target for therapy
TLDR
Elevated plasma FFA levels have been shown to account for up to 50% of insulin resistance in obese patients with T2DM, and lowering of FFA in these patients could be a new and promising approach to manage T2 DM. Expand
High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.
TLDR
Both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs, which may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome. Expand
IKK-β links inflammation to obesity-induced insulin resistance
TLDR
The importance of liver cell IKK-β in hepatic insulin resistance and the central role of myeloid cells in development of systemic insulin resistance are demonstrated and it is suggested that inhibition of Ikk-β, especially in myeloids cells, may be used to treat insulin resistance. Expand
Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation
  • E. Tomás, T. Tsao, +5 authors N. Ruderman
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
Both in vivo and in vitro, activation of AMPK was the first effect of gACRP30 and was transient, whereas alterations in malonyl CoA and ACC occurred later and were more sustained, indicating that gAC RP30 most likely exerts its actions on muscle fatty acid oxidation by inactivating ACC via activation ofAMPK and perhaps other signal transduction proteins. Expand
Acute reversal of lipid-induced muscle insulin resistance is associated with rapid alteration in PKC-theta localization.
TLDR
Results provide further support for an association between PKC-theta muscle cellular localization and lipid-induced muscle insulin resistance and stress the labile nature of high-fat diet-induced insulin resistance in the rat. Expand
...
1
2
3
4
...