Fig. 2

Summary of endotoxin effects on adipocytes. Lipopolysaccharide (LPS) is recognized by CD14 molecules, and its effects depend on TLR4 signaling. The activation of MYD88 and TRIF pathways result in enhanced expression of transcription factors (nuclei) including NF-κB and IRF. NF-κB enhances the expression of pro-inflammatory cytokines leading to inflammation (1). Inflammation induces endoplasmic reticulum (ER) stress (2), leading to the activation of unfolded protein response (UPR). Products from the UPR such as IREA1 are necessary for ERK1-mediated activation of hormone-sensitive lipase (HSL). Lipolysis (3) is also activated by TLR4 signaling by enhancing PKA and the subsequent activation of HSL and adipose triglyceride lipase (ATGL). Inflammation and UPR contribute to elevated oxidative stress (4) by higher production of reactive oxygen species (ROS). Inflammation is the main contributor of mitochondrial dysfunction (5), leading to lower production of ATP. Inflammation inhibits the activity of peroxisome proliferator activated receptor gamma (PPARγ), resulting in lower adipogenic capacity (6). Together, (1) Inflammation, (2) ER stress, (3) Lipolysis, (4) Oxidative stress, and (5) Mitochondrial dysfunction lead to (7) Insulin resistance. Created with BioRender.com