FIGURE 3.

NADPH oxidase-derived ROS signaling and cellular effects in MetS. ROS derived from NADPH oxidases are involved in the inflammatory responses associated with MetS, in macrophages, for example. ROS stimulate NF-κB, via MAPK and IKKα/β, and AP-1, via ASK1 and JNK, which promote the transcription of proinflammatory genes (e.g., TNF, IL-1β, IL-6, iNOS, COX2, and INF), resulting in inflammatory responses associated with MetS. ROS also activate Nrf2 to induce genes that regulate intermediary metabolism (e.g., G6PD, PGD, TKT, PPAT, IDH1, and CPT1) (only some genes are listed). The antioxidant effect and modulation of metabolism are adaptive responses to ROS-induced proinflammatory responses and altered metabolism. ROS exert a wide range of effects such as inflammation, insulin resistance, adipocyte proliferation, altered metabolism, among others in diverse cells, including macrophages, endothelial cells, vascular cells, adipocytes, preadipocytes, and epithelial cells. The ROS-mediated signaling and cellular efforts are cell type-specific that are overlapping. For simplicity and clarity, only part of signaling and cellular effects in macrophages are illustrated. AP-1, activator protein 1; ASK1, apoptosis signal-regulating kinase 1; COX2, cyclooxygenase-2; CPT1, carnitine palmitoyltransferase 1; G6PD, glucose-6-phosphate dehydrogenase; IDH1, isocitrate dehydrogenase 1; IL, interleukin; iNOS, inducible nitric oxide synthase; JNK, c-Jun N-terminal kinases; Keap1, Kelch-like ECH-associated protein 1; IKK, IκB kinase; MAPK, mitogen-activated protein kinase; MetS, metabolic syndrome; PM, plasma membrane and other cellular membranes; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2, nuclear factor-erythroid 2 p45-related factor 2; PGD, 6-phosphogluconate dehydrogenase; PPAT, phosphoribosyl pyrophosphate aminotransferase; TKT, transketolase.