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Inflammation and lipid signaling in the etiology of insulin resistance - PubMed

  • ️Sun Jan 01 2012

Review

Inflammation and lipid signaling in the etiology of insulin resistance

Christopher K Glass et al. Cell Metab. 2012.

Abstract

Inflammation and lipid signaling are intertwined modulators of homeostasis and immunity. In addition to the extensively studied eicosanoids and inositol phospholipids, emerging studies indicate that many other lipid species act to positively and negatively regulate inflammatory responses. Conversely, inflammatory signaling can significantly alter lipid metabolism in the liver, adipose tissue, skeletal muscle, and macrophage in the context of infection, diabetes, and atherosclerosis. Here, we review recent findings related to this interconnected network from the perspective of immunity and metabolic disease.

Copyright © 2012 Elsevier Inc. All rights reserved.

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Figures

Figure 1
Figure 1. The effects of fatty acids on inflammation and insulin resistance

Saturated fatty acids (SFAs) stimulate inflammatory pathways through Tlr4 dependent and independent mechanisms. SFAs are also precursors for ceramide biosynthesis, and inflammatory pathway stimulation by SFAs, as well as cytokines, induces the enzymes which produce ceramide, providing two mechanisms for increased ceramide content. Omega 3 FAs produce anti-inflammatory effects by stimulating GPR120 and production of resolvins and protectins. Omega 6 FAs can be proinflammatory through their metabolism to leukotrienes and prostaglandins.

Figure 2
Figure 2

(A) Tlr4 and TNF receptor signaling stimulates the TAK1/TAB1 complex which then activates IKKβ and MKK4 to stimulate the downstream NFκB and JNK1 inflammatory pathways. (B) Omega 3 FAs activate GPR120 causing it to associate with β arrestin-2. The GPR120•β arrestin-2 complex then undergoes endocytosis and the internalized β arrestin-2 binds to TAB1, “stealing” it from the TAK1 complex, causing TAK1 inactivation with inhibition of subsequent downstream proinflammatory signaling. Adapted from (Oh et al., 2010).

Figure 3
Figure 3

Impact of inflammation on lipid metabolism. Inducers and amplifiers of inflammation include ligands for pattern recognition receptors (e.g. LPS), cytokines (e.g., Il1β) and saturated fatty acids (SFAs). Each of these inflammatory stimuli influence lipid metabolism in liver, skeletal muscle and adipose tissue by acting on both parenchymal cells and resident immune cells. Although some effects are seen in all three organs (e.g., increased TG hydrolysis), other effects may be organ-specific (e.g., increased fatty acid biosynthesis in liver).

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