Molecular Targets Related to Inflammation and Insulin Resistance and Potential Interventions

Figure 2

Inflammatory pathways activated during obesity and their cross talk with insulin signaling. Different signals act directly through membrane (e.g., toll-like receptors [TLRs] and cytokine receptors) and intracellular proteins (inflammasomes) or indirectly by their effect on cell organelles such as mitochondria and endosomal reticulum and generation of metabolites (e.g., ceramides and other lipid mediators) to activate inflammatory pathways. Transcription factor such as nuclear factor κB (NFκB), activator protein-1 (AP-1), and signal transducers and activators of transcription (STAT) are activated downstream to these pathways and lead to the expression of proteins that inhibit insulin signaling and induce a pro-inflammatory state by recruiting and activating immune cells. AT, adipose tissue; DAMPS, damage associated molecular patterns; ER, endoplasmic reticulum; HIF-1, hypoxia factor-1; IAPP, islet amyloid polypeptide; PAMPS, pathogen associated molecular patterns; ROS, reactive oxygen species; SFAs, saturated fatty acids; SOCS, suppressor of cytokine signaling; TAK, transforming growth factor β-activated kinase.