Free fatty acid infusion in male rats caused hepatic insulin resistance, increased hepatic diacylglycerol content (+210%), and activated the proinflammatory NF-kappaB pathway.
Free fatty acids induce hepatic insulin resistance and initiate inflammatory processes in the liver via the NF-κB pathway in a rat model.
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 proinflammatory nuclear factor-kappaB (NF-kappaB) pathway (IkappaB kinase-beta, +640%; IkappaB-alpha, -54%; and NF-kappaB, +73%), and increased expression of inflammatory cytokines (tumor necrosis factor-alpha, +1,700% and interleukin-1beta, +440%) and plasma levels of monocyte chemoattractant protein-1 (+220%). We conclude that FFAs caused hepatic insulin resistance, which can produce overproduction of glucose and hyperglycemia, and initiated inflammatory processes in the liver that could potentially result in the development of steatohepatitis.
Boden et al. (Thu,) conducted a other in Hepatic insulin resistance. Lipid/heparin infusion (to raise plasma free fatty acids) vs. Without infusion (to lower plasma free fatty acids) was evaluated on Hepatic insulin resistance and activation of proinflammatory pathways. Free fatty acid infusion in male rats caused hepatic insulin resistance, increased hepatic diacylglycerol content (+210%), and activated the proinflammatory NF-kappaB pathway.
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