Figure 3.

The possible mechanisms underlying the effects of H₂ on metabolic diseases. The figure demonstrates the potential mechanisms underlying the effects of H₂ on metabolic diseases, including scavenging or inhibiting generation of ROS; activating Mito-K-ATP channels; promoting the transport of fatty acids into mitochondria; as well as the pathways involved in the anti-oxidative, anti-inflammatory, and anti-apoptotic effects, and suppression of ER stress and activation of autophagy, including the Nrf2/ARE/HO-1, PARP-1/AIF, HO-1/SIRT1/p53, JNK/p38 MAPK/p53, Akt/FoxO1/PGC-1α/PPARα/γ, NF-kB-mediated, and PERK-mediated UPR pathways. Abbreviations: Mito-K-ATP, mitochondrial ATP-sensitive potassium; SIRT1, Sirtuin1; LC3-II, microtubule-associated protein light chain 3-II; HO-1, heme oxygenase-1; ATF6, activating transcription factor 6; GRP78/BiP, glucose-regulated protein 78/binding immunoglobulin protein; PERK, proteins R (PKR)-like endoplasmic reticulum kinase; 4-HNE, 4-hydoxy-2-nonenal; FoxO1, forkhead box O1; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1 alpha; PPARα/γ, peroxisome proliferator-activated receptor alpha/gamma; Nrf2, nuclear factor erythroid 2-related factor 2; ARE, antioxidant responsive element; NF-kB, nuclear factor-kappaB; IkBα, inhibitory subunit of NF-kB alpha; JNK/p38 MAPK, c-Jun N-terminal kinase/p38 mitogen-activated protein kinase; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; PARP-1, poly (ADP-ribose) polymerase-1; PAR, poly(ADP-ribose); AIF, apoptosis-inducing factor; CAT, catalase; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; FGF21, fibroblast growth factor 21.