ABSTRACT
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.
Subject(s)
AMP-Activated Protein Kinases , Hyperlipidemias , Ketoglutaric Acids , NF-E2-Related Factor 2 , Oxidative Stress , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Signal Transduction , Animals , Hyperlipidemias/metabolism , Hyperlipidemias/drug therapy , Hyperlipidemias/complications , Mice , Oxidative Stress/drug effects , Humans , NF-E2-Related Factor 2/metabolism , AMP-Activated Protein Kinases/metabolism , Ketoglutaric Acids/metabolism , Ketoglutaric Acids/pharmacology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Signal Transduction/drug effects , Hep G2 Cells , Mitochondria/metabolism , Mitochondria/drug effects , Male , Lipid Metabolism/drug effects , Hepatocytes/metabolism , Hepatocytes/drug effects , Fatty Liver/metabolism , Fatty Liver/etiology , Fatty Liver/drug therapy , Fatty Liver/prevention & control , Fatty Liver/pathology , Disease Models, Animal , Liver/metabolism , Liver/drug effects , Liver/pathologyABSTRACT
The nature always offers amazing inspiration, where it is highly desirable to endow coatings on marine equipment with powerful functions. An excellent example is slippery zone of Nepenthes pitcher, which possesses novel liquid-repellent and self-cleaning performance. Therefore, this study presents an efficient fabrication method to prepare a novel coating. The coatings were fabricated by designing biomimetic textures extracted from the lunate bodies of slippery zone on polydimethylsiloxane (PDMS) and then grafting Dictyophora indusiata polysaccharide (DIP) modifier. The as-prepared slippery coatings exhibited outstanding antifouling properties against kinds of daily life pollutants such as Chlorella and coffee. This synergistic strategy was proposed combined with environmentally friendly modifier grafting and heterogeneous microstructure on the surface to broaden new probabilities for manufacturing slippery coatings with incredible protective functionality.
ABSTRACT
Aims: Drug resistance in ovarian cancer (OC) cells often leads to recurrence, metastasis, and high mortality rates among OC patients. Hydroxytyrosol (HT) has been reported to inhibit the proliferation of ovarian and other types of cancer cells. Here we synthesized a novel cyclohexane-hydroxytyrosol derivative (Chx-HT) for enhanced anticaner efficacy. We examined the growth-suppressing effect of Chx-HT on OC cells in vitro and in a xenograft mouse model and investigated the underlying mechanism. Results: We demonstrated that Chx-HT inhibits proliferation, promotes apoptosis, and remodels glucose and lipid metabolism by reducing fatty acid ß-oxidation while increasing glycolysis, de novo fatty acid synthesis (FAS), and lipid droplet (LD) accumulation, impairs mitochondrial respiration, and induces oxidative stress both in vitro and in vivo. In addition, Chx-HT blocks autophagic flux by obstructing the maturation of lysosomal cathepsins in the late stage, but also activates autophagy through the p-AMPK/p-mTOR/p-ULK1 pathway in response to energy deficit. Innovation and Conclusion: Reactive oxidative species (ROS) play a critical role in mediating the effects of Chx-HT on proliferation, apoptosis, autophagy, tricarboxylic acid (TCA) cycle, fatty acid ß-oxidation, and mitochondrial respiration, and the autophagic activation underlies the effects of Chx-HT on glycolysis, de novo FAS, and LD accumulation in OC cells. Cotreating OC cells with Chx-HT and autophagic inhibitor or glycolytic inhibitor results in an additive inhibition of proliferation. Our study indicates that Chx-HT stands for a promising OC therapeutic by ROS and autophagy blockade-mediated metabolic remodeling.
ABSTRACT
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.
ABSTRACT
Relatively little psychology research has investigated racial-ethnic socialization processes in multiethnic-racial families despite the fact that more than 1 in 7 children born in the United States today have parents from different ethnic-racial backgrounds. The present study seeks to contribute to the extant research by exploring how parents in multiethnic-racial families seek to help their children access and benefit from two (or more) sets of cultural assets. Accordingly, this study considers key themes about cultural socialization that emerged in qualitative interviews with parents in multiethnic-racial families (n = 37). Key themes emerging from these interviews included the importance of both co-parents: (a) putting in the time and effort to learn about each other's cultures and cultural practices; (b) being reflective about the practices, values, and traditions that were and were not important to them to share with their children; and (c) protecting their children from racial micro-aggressions in a variety of settings by advocating for the recognition, inclusion, and appreciation of their children's multiple ethnic-racial heritages. There is such a paucity of research on cultural socialization approaches in multiethnic-racial families that these perspectives from parents offer both valuable building blocks for future research efforts as well as practical guidance to the growing number of multiethnic-racial families in the United States and elsewhere.