Catabolism of (2E)-4-Hydroxy-2-nonenal via ω- and ω-1-Oxidation Stimulated by Ketogenic Diet

Jin, Zhicheng; Berthiaume, Jessica M.; Li, Qingling; Henry, Fabrice; Huang, Zhong; Sadhukhan, Sushabhan; Gao, Peng; Tochtrop, Gregory P.; Puchowicz, Michelle A.; Zhang, Guo Fang

doi:10.1074/jbc.m114.602458

Cited by 17 publications

(16 citation statements)

References 47 publications

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“…9 ). All together these results indicate an important catabolism of HNE, given by oral or parenteral route, through β-oxidation of HNA and possibly also through ω-oxidation of HNA and further β-oxidation steps originating from the carbon 9 of HNA as recently reported by some authors [23] .…”

Section: Resultssupporting

confidence: 83%

“…This metabolite could originate from a β-oxidation step originating from the carbon 9 of HNA, as we observed the “twin compound” still retaining the stable isotope labeling on carbon 1 and 2 (ion at m/z 175), precluding any possibility of β-oxidation step on the carbons 1 and 2 of HNA. The presence of this metabolite accounting for 2% of urinary radioactivity reinforces the HNE disposition pathway evidenced recently by Jin et al [23] .…”

Section: Resultssupporting

confidence: 83%

“…This saturation pathway could involve NADPH-dependent alkenal/one oxidoreductase as reported by some authors [31] . 4,8-Hydroxy-nonanoic acid and 4,9-hydroxy-nonanoic acid have been reported by Jin et al [23] and by Laurent et al [20] , as metabolites of HNE.…”

Section: Resultsmentioning

confidence: 85%

“…Such chemical structure has not been evidenced in our previous studies. However, ω −1 oxidation has been reported by Jin et al [23] .…”

Section: Resultsmentioning

confidence: 92%

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“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats

et al. 2015

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4-Hydroxynonenal (HNE) is a cytotoxic and genotoxic lipid oxidation secondary product which is formed endogenously upon peroxidation of cellular n-6 fatty acids.However, it can also be formed in food or during digestion, upon peroxidation of dietary lipids. Several studies have evidenced that we are exposed through food to significant concentrations of HNE that could pose a toxicological concern. It is then of importance to known how HNE is metabolized after oral administration. Although its metabolism has been studied after intravenous administration in order to mimick endogenous formation, its in vivo fate after oral administration had never been studied.In order to identify and quantify urinary HNE metabolites after oral administration in rats, radioactive and stable isotopes of HNE were used and urine was analyzed by radio-chromatography (radio-HPLC) and chromatography coupled with High Resolution Mass Spectrometry (HPLC–HRMS).Radioactivity distribution revealed that 48% of the administered radioactivity was excreted into urine and 15% into feces after 24 h, while 3% were measured in intestinal contents and 2% in major organs, mostly in the liver. Urinary radio-HPLC profiles revealed 22 major peaks accounting for 88% of the urinary radioactivity. For identification purpose, HNE and its stable isotope [1,2-13C]-HNE were given at equimolar dose to be able to univocally identify HNE metabolites by tracking twin peaks on HPLC–HRMS spectra. The major peak was identified as 9-hydroxy-nonenoic acid (27% of the urinary radioactivity) followed by classical HNE mercapturic acid derivatives (the mercapturic acid conjugate of di-hydroxynonane (DHN-MA), the mercapturic acid conjugate of 4-hydroxynonenoic acid (HNA-MA) in its opened and lactone form) and by metabolites that are oxidized in the terminal position. New urinary metabolites as thiomethyl and glucuronide conjugates were also evidenced. Some analyses were also performed on feces and gastro-intestinal contents, revealing the presence of tritiated water that could originate from beta-oxidation reactions.

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 85%

“…Such chemical structure has not been evidenced in our previous studies. However, ω −1 oxidation has been reported by Jin et al [23] .…”

Section: Resultsmentioning

confidence: 92%

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“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats

et al. 2015

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“…Isotope labelling experiments have shown that KD therapy induces cytochrome P450 4A-dependent ω- and ω-1-hydroxylation of reactive lipid species, a novel mechanism that might contribute to the anti-inflammatory properties of KD therapy [42]. …”

Section: Oxidative Stressmentioning

confidence: 99%

New insights into the mechanisms of the ketogenic diet

Boison

2017

Current Opinion in Neurology

209

150

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Purpose of review High-fat, low-carbohydrate ketogenic diets (KDs) have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of KDs has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of KD therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by KD therapies. Recent findings KDs act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium chain triclycerides, contributes to seizure control through direct AMPA receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. KD therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Summary KD therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

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Non-coding RNAs Related to Lipid Metabolism and Non-alcoholic Fatty Liver Disease

Holvoet

2021

Non-Coding RNAs at the Cross-Road of Cardiometabolic Diseases and Cancer

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Catabolism of (2E)-4-Hydroxy-2-nonenal via ω- and ω-1-Oxidation Stimulated by Ketogenic Diet

Cited by 17 publications

References 47 publications

“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats

“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats

New insights into the mechanisms of the ketogenic diet

Non-coding RNAs Related to Lipid Metabolism and Non-alcoholic Fatty Liver Disease

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