Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition

Kishino, Shigenobu; Takeuchi, Mitsuaki; Park, Si Bum; Hirata, Akiko; Kitamura, Nahoko; Kunisawa, Jun; Kiyono, Hiroshi; Iwamoto, Ryo; Isobe, Yosuke; Arita, Makoto; Arai, Hiroyuki; Ueda, Kazumitsu; Shima, Jun; Takahashi, Satoshi; Yokozeki, Kenzo; Shimizu, Sakayu; Ogawa, Jun

doi:10.1073/pnas.1312937110

Cited by 318 publications

(300 citation statements)

References 30 publications

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“…MUFAs (namely, oleic acid -C18:1 c9) were present in both waxes at identical amount (~30 µg FA/mg sample); in contrast, PUFAs, namely, eicosapentaenoic acid (EPA: C22:5 n3), were at higher concentrations in Carnauba wax than in the Witepsol one. Since PUFAs are considered to have more potential for toxicity, 48 when compared with SFA, waxes should be carefully inspected regarding toxicological effects, namely, Carnauba wax, which showed a higher content of these FAs. Our results demonstrate a decreased PUFA content in feces in all SLN-treated groups.…”

Section: Discussionmentioning

confidence: 99%

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Madureira

Nunes

Fernandes

et al. 2016

IJN

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Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

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Section: Discussionmentioning

confidence: 99%

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Madureira

Nunes

Fernandes

et al. 2016

IJN

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“…In the course of these studies, numerous PUFA-transforming bacteria, such as Butyrivibrio fi brisolvens ( 4 ), Lactobacillus plantarum (20)(21)(22)(23), and Bifi dobacterium breve ( 19 ), have been isolated, and their metabolic pathways of C 18 PUFAs, such as LA and ␣ -linolenic acid, have been revealed. However, the ability to transform C 20 and C 22 PUFAs has not been studied in detail, although there have been several reports that EPA and DHA are hydrogenated in the rumen in vivo ( 26 ) and disappear during incubations in vitro with mixed ruminal microorganisms ( 27,28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Further, we have revealed that lactic acid bacteria produce unique PUFAs from various C 18 PUFAs through partial biohydrogenation (21)(22)(23). Thus, the biohydrogenation of C 18 PUFAs has been widely studied.…”

Section: Gc-ms Analysismentioning

confidence: 99%

Biohydrogenation of C20 polyunsaturated fatty acids by anaerobic bacteria

Sakurama

Kishino

Mihara

et al. 2014

Journal of Lipid Research

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“…at 37°C for 2 h. Lipid extraction was performed as described previously [7]. The extracted lipids were dissolved in 2 mL of methanol and 3 mL of benzene and then methylated with 150 lL of 1% diazomethane at room temperature for 30 min.…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…The action of the gut-bacterial fatty acid saturation metabolism modifies the fatty acid composition of the host and is expected to improve human health by altering lipid metabolism, which is related to the onset of metabolic syndrome [7]. Interestingly, the enzymes involved in the gut-bacterial fatty acid saturation metabolism catalyze modification reactions of free fatty acids without CoA or ACP.…”

Section: Introductionmentioning

confidence: 99%

Structure and reaction mechanism of a novel enone reductase

et al. 2015

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Recently, a novel gut‐bacterial fatty acid metabolism, saturation of polyunsaturated fatty acid, that modifies fatty acid composition of the host and is expected to improve our health by altering lipid metabolism related to the onset of metabolic syndrome, was discovered in Lactobacillus plantarum AKU 1009a. Enzymes constituting the pathway catalyze sequential reactions of free fatty acids without CoA or acyl carrier protein. Among these enzymes, CLA‐ER was identified as an enone reductase that can saturate the C=C bond in the 10‐oxo‐trans‐11‐octadecenoic acid (KetoB) to produce 10‐oxo‐octadecanoic acid (KetoC). This enzyme is the sole member of the NADH oxidase/flavin reductase family that has been identified to exert an enone reduction activity. Here, we report both the structure of holo CLA‐ER with cofactor FMN and the KetoC‐bound structure, which elucidate the structural basis of enone group recognition of free fatty acids and provide the unique catalytic mechanism as an enone reductase in the NADH oxidase/flavin reductase family. A ‘cap’ structure of CLA‐ER underwent a large conformational change upon KetoC binding. The resulting binding site adopts a sandglass shape and is positively charged at one side, which is suitable to recognize a fatty acid molecule with enone group. Based on the crystal structures and enzymatic activities of several mutants, we identified C51, F126 and Y101 as the critical residues for the reaction and proposed an alternative electron transfer pathway of CLA‐ER. These findings expand our understanding of the complexity of fatty acid metabolism. Database The atomic coordinates have been deposited in the Protein Data Bank (PDB), http://www.pdb.org (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=4QLX, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=4QLY)

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Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition

Cited by 318 publications

References 30 publications

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Biohydrogenation of C20 polyunsaturated fatty acids by anaerobic bacteria

Structure and reaction mechanism of a novel enone reductase

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