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Switching acidity on manganese oxide catalyst with acetylacetones for selectivity-tunable amines oxidation
No full textThe design of metal oxide catalysts predominantly focuses on the composition or geometry engineering to enable optimized reactivity on the surface. Despite the numerous reports investigating the surface chemisorption of organic molecules on metal oxides, insights into how adsorption of organic modifiers can be exploited to optimize the catalytic properties of metal oxides are lacking. Herein, we describe the use of enolic acetylacetones to modify the surface Lewis acid properties of manganese oxide catalysts. The acetylacetone modification is stable under the reaction conditions and strongly influences the redox-acid cooperative catalysis of manganese oxides. This enables a rational control of the oxidation selectivity of structurally diverse arylmethyl amines to become switchable from nitriles to imines
Metabolomics profiling of metformin-mediated metabolic reprogramming bypassing AMPK alpha
No full textBackground: Metformin is a first-line drug for treating type 2 diabetes and has gained considerable interest as a potential anticancer agent. Increasing evidence suggests that metformin antagonizes diabetes and tumors through disrupting metabolic homeostasis and altering energy state. However, whether AMP activated protein kinase (AMPK) contributes to such effects of metformin remains controversial.
Methods: We performed integrative metabolomics analyses to systematically examine the effects of metformin on metabolic pathways in Prkaa1 wild type (WT) and knock-out (KO) mouse embryonic fibroblast (MEF) cells as well as human cells based on gas chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry (CE-MS).
Results: Metformin treatment induced metabolic reprogramming and reduced the energy state of both Prkaa1 WT and KO MEF cells, as evidenced by suppressed tricarboxylic acid (TCA) cycle, elevated lactate production as well as decreased NAD(+)/NADH ratio. Additionally, metabolic flux analysis also showed that metformin Ampk alpha-independently increased metabolic flux from glucose to lactate and decreased metabolic flux from acetyl-CoA to TCA cycle as well as from pyruvate to malate. Moreover, metformin Ampk alpha-dependently upregulated P-Acc but Ampk alpha-independently inhibited the levels of P-mTor, P-S6, Lc3,Atgl and P-Erk in MEF cells. Similarly, we demonstrated that a commonly used AMPK agonist 5-Aminoimidazolc-4-carboxamidc ribonudeotide (AICAR) and fetal bovine serum (FBS) starvation, as a common model for energy stress, both led to Ampk alpha-independent metabolism alterations in MEF cells. Furthermore, these effects of metformin were also confirmed in human hepatocellular carcinoma (HCC) cells as well as in MCF10A shControl and shPRKAA1 cells. Importantly, we found that metformin could obviously inhibit colony conformation of HCC cells in an Ampk alpha-independent manner.
Conclusions: Our data highlight a comprehensive view of metabolic reprogramming mediated by metformin as well as AICAR. These observations suggest that metformin could affect cellular metabolism largely bypassing Ampk alpha, and may provide a new insight for its dinical usage. (C) 2018 Elsevier Inc. All rights reserved
Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages
No full textDisordered intestinal metabolism is highly correlated with atherosclerotic diseases. Resveratrol protects against atherosclerotic diseases. Accordingly, this study aims to discover novel intestinal proatherosclerotic metabolites and potential therapeutic targets related to the anti-atherosclerotic effects of resveratrol. An untargeted metabolomics approach was employed to discover novel intestinal metabolic disturbances during atherosclerosis and resveratrol intervention. We found that multiple intestinal metabolic pathways were significantly disturbed during atherosclerosis and responsive to resveratrol intervention. Notably, resveratrol abolished intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice. Meanwhile, oleate accumulation was one of the most prominent alterations in intestinal metabolism. Moreover, resveratrol attenuated oleate-triggered accumulation of total cholesterol, esterified cholesterol and neutral lipids in mouse RAW 264.7 macrophages by activating ABC transporter A1/G1-mediated cholesterol efflux through PPAR (peroxisome proliferator-activated receptor) alpha/gamma activation. Furthermore, we confirmed that PPAR alpha and PPAR gamma activation by WY14643 and pioglitazone, respectively, alleviated oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids by accelerating ABC transporter A1/G1-mediated cholesterol efflux. This study provides the first evidence that resveratrol abolishes intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice, and that resveratrol suppresses oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids in macrophages by activating PPAR alpha/gamma signalling
