α-Ketoglutarate prevents hyperlipidemia-induced fatty liver mitochondrial dysfunction and oxidative stress by activating the AMPK-pgc-1α/Nrf2 pathway.

α-Ketoglutarate (AKG), a crucial intermediate in the tricarboxylic acid cycle, has been demonstrated to mitigate hyperlipidemia-induced dyslipidemia and endothelial damage. While hyperlipidemia stands as a major trigger for non-alcoholic fatty liver disease, the protection of AKG on hyperlipidemia-induced hepatic metabolic disorders remains underexplored. This study aims to investigate the potential protective effects and mechanisms of AKG against hepatic lipid metabolic disorders caused by acute hyperlipidemia. Our observations indicate that AKG effectively alleviates hepatic lipid accumulation, mitochondrial dysfunction, and loss of redox homeostasis in P407-induced hyperlipidemia mice, as well as in palmitate-injured HepG2 cells and primary hepatocytes. Mechanistic insights reveal that the preventive effects are mediated by activating the AMPK-PGC-1α/Nrf2 pathway. In conclusion, our findings shed light on the role and mechanism of AKG in ameliorating abnormal lipid metabolic disorders in hyperlipidemia-induced fatty liver, suggesting that AKG, an endogenous mitochondrial nutrient, holds promising potential for addressing hyperlipidemia-induced fatty liver conditions.

Hydrogen: A Rising Star in Gas Medicine as a Mitochondria-Targeting Nutrient via Activating Keap1-Nrf2 Antioxidant System.

The gas molecules O2, NO, H2S, CO, and CH4, have been increasingly used for medical purposes. Other than these gas molecules, H2 is the smallest diatomic molecule in nature and has become a rising star in gas medicine in the past few decades. As a non-toxic and easily accessible gas, H2 has shown preventive and therapeutic effects on various diseases of the respiratory, cardiovascular, central nervous system, and other systems, but the mechanisms are still unclear and even controversial, especially the mechanism of H2 as a selective radical scavenger. Mitochondria are the main organelles regulating energy metabolism in living organisms as well as the main organelle of reactive oxygen species' generation and targeting. We propose that the protective role of H2 may be mainly dependent on its unique ability to penetrate every aspect of cells to regulate mitochondrial homeostasis by activating the Keap1-Nrf2 phase II antioxidant system rather than its direct free radical scavenging activity. In this review, we summarize the protective effects and focus on the mechanism of H2 as a mitochondria-targeting nutrient by activating the Keap1-Nrf2 system in different disease models. In addition, we wish to provide a more rational theoretical support for the medical applications of hydrogen.

α-Ketoglutarate Attenuates Hyperlipidemia-Induced Endothelial Damage by Activating the Erk-Nrf2 Signaling Pathway to Inhibit Oxidative Stress and Mitochondrial Dysfunction.

Aims: α-Ketoglutarate (AKG) is an intermediate of the tricarboxylic acid cycle and a key hub linking amino acid metabolism and glucose oxidation. Previous studies have shown that AKG improved cardiovascular diseases such as myocardial infarction and myocardial hypertrophy through antioxidant and lipid-lowering characteristics. However, its protective effect and mechanism on endothelial injury caused by hyperlipidemia have not been elucidated yet. In this study, we tested whether AKG possesses protective effects on hyperlipidemia-induced endothelial injury and studied the mechanism. Results: AKG administration both in vivo, and in vitro significantly suppressed the hyperlipidemia-induced endothelial damage, regulated ET-1 and nitric oxide levels, and reduced the inflammatory factor interleukin-6 and matrix metallopeptidase-1 by inhibiting oxidative stress and mitochondrial dysfunction. The protective effects were achieved by the mechanism of activating the Nrf2 phase II system through the ERK signaling pathway. Innovation: These results reveal the role of the AKG-ERK-Nrf2 signaling pathway in the prevention of hyperlipidemia-induced endothelial damage, and suggest that AKG, as a mitochondria-targeting nutrient, is a potential drug for the treatment of endothelial damage in hyperlipidemia. Conclusion: AKG ameliorated the hyperlipidemia-induced endothelial damage and inflammatory response by inhibiting oxidative stress and mitochondrial dysfunction. Antioxid. Redox Signal. 39, 777-793.

Rational construction of triangle-like nickel-cobalt bimetallic metal-organic framework nanosheets arrays as battery-type electrodes for hybrid supercapacitors.

Reasonably designing self-supported metal-organic framework (MOF) nanoarrays is profound for applications in energy storage and conversion. Herein, we construct a triangle-like nickel-cobalt bimetallic metal-organic framework nanosheet array on nickel foam (NiCo-MOF/NF) via facile one-step hydrothermal reaction, served as battery-like electrode material for hybrid supercapacitors. By adjusting the molar ratio of Ni and Co, the optimal NiCo-MOF/NF with Ni/Co = 3:2 (3-2 NiCo-MOF/NF) produces an impressive specific capacity of 1003.5 C/g (2230 F/g) at 1 A/g, surpassing most of the previously reported MOF based electrode materials. The superior electrochemical performances may be related to their 3D well-aligned MOF nanosheets arrays, which provides enlarged electroactive areas. Meanwhile, the tight junction of electrode materials and conductive substrate nickel foam (NF) can guarantee their sufficient electric contact, contributing to fast electron transfer from electrodes to conductive substrates. Finally, a hybrid supercapacitor fabricated by the 3-2 NiCo-MOF/NF against active carbon (AC) delivers an advantageous energy density of 34.3 Wh/kg at a power density of 375 W/kg. These results certificate that such bimetallic NiCo-MOF nanosheets arrays hold great potential as novel electrode materials for hybrid supercapacitors.