Fig. 3

Induction of inflammatory signals in proinflammatory macrophages and their connection with insulin pathways. a After translocation of gut bacteria to other tissues, the bacterial lipopolysaccharides (LPS) in the circulation and organs activate the transcription of cytokines via Toll-like receptor (TLR)4. Activated TLR4 mediates inflammatory signals involving myeloid differentiation primary response gene 88 (MyD88)-dependent pathways. The downstream responses trigger the activation of mitogen-activated protein kinase (MAPK) pathways, including those involving extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), c-Jun-N-terminal kinases (JNK), p38, and inhibitor of IκB kinase complex (IKKβ). These pathways participate in the activation of transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1) and cytokine production. ERK1/2 and JNKs are also involved in the induction of insulin signaling pathways. b Pattern-recognition receptors such as TLR4, TLR2, and TLR8 are activated by LPS, cytokines, or lipotoxicity. The intracellular nucleotide oligomerization domain (NOD)-like receptors also recognize LPS, which leads to induction of thioredoxin-interacting protein (which is encoded by TXNIP) and recruitment of other effector molecules such as those that are components of inflammasome pathways [28]. Inflammasomes are multiprotein complexes composed of three proteins: nucleotide-binding domain leucine-rich repeat containing (NLR) protein, adaptor protein ASC, and caspase-1. Inflammasome activation contributes to the maturation of the cytokines interleukin (IL)-1β and IL-8