Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice

Rossmeisl, Martin; Medříková, Daša; Schothorst, Evert M. van; Pavlisova, Jana; Kuda, Ondřej; Hensler, Michal; Bardová, Kristina; Flachs, Pavel; Staňková, Barbora; Vecka, Marek; Tvrzická, E; A, Žák; Keijer, Jaap; Kopecký, Jan

doi:10.1016/j.bbalip.2013.11.010

Cited by 74 publications

(82 citation statements)

References 55 publications

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“…Moreover, the offspring of mothers maintained on a DHAenriched diet showed a significant downregulation of the classical lipogenic transcription factor, Srebp-1c, and its target genes, Fas and Scd1 (Fig. 7A-C), which supports the concept of DHA as a suppressor of lipogenesis described previously in adult animals (25)(26)(27). Because our data suggests that the DHA level in the offspring is a result of a dynamic interplay between hepatic (supplemental Fig.…”

Section: Pups Fed By Elovl2supporting

confidence: 69%

Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

Pauter

Trattner

González-Bengtsson

et al. 2017

Journal of Lipid Research

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Section: Pups Fed By Elovl2supporting

confidence: 69%

Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

Pauter

Trattner

González-Bengtsson

et al. 2017

Journal of Lipid Research

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“…Surprisingly, however, mice fed fi sh oil had low expression of genes encoding cholesterol biosynthesis enzymes despite high levels of activated SREBP2. Saturated lipids have been shown to induce cholesterol biosynthesis ( 27 ), while lipids rich in polyunsaturated fatty acids have been shown to reduce cholesterol biosynthesis in the liver ( 28 ). Moreover, in vitro experiments have previously demonstrated that the polyunsaturated fatty acid, DHA, activates SREBP2 without increasing cholesterol biosynthesis ( 29,30 ), suggesting that polyunsaturated fatty acids regulate cholesterol biosynthesis through alternative mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism

Caesar

Nygrén

Orešič

et al. 2016

Journal of Lipid Research

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This article is available online at http://www.jlr.org dyslipidemia, increased hepatic lipogenesis, and liver steatosis ( 1 ). In contrast, consumption of polyunsaturated fatty acids is associated with a lean and metabolically healthy phenotype ( 2-4 ). Emerging evidence suggests that some of the effects of dietary lipids on host metabolism may be mediated by modifi cations of the gut microbiota composition, which result in altered metabolic properties of the gut microbiota ( 5-8 ) and/or by alterations in gut integrity, which affect the extent of leakage of microbially derived metabolites into the circulation ( 6 ).Metabolites produced by the gut microbiota may be utilized as a source of energy by the host or may act as signaling molecules that infl uence host metabolism ( 8 ). These metabolites can have a local effect in the intestine, but may also be transferred from the gut into the circulation, thereby affecting peripheral tissues ( 8 ). Indeed, germfree (GF) mice have been shown to have improved glucose sensitivity and to be protected against obesity and dyslipidemia ( 9-12 ), exemplifying the systemic importance of the microbiota. Because of its proximity to the gastrointestinal tract, the liver is strongly affected by the microbiota, and bacterial status has been shown to affect both hepatic lipid biosynthesis ( 9 ) and lipid degradation ( 13 ). Several mechanisms linking bacterial metabolic processes with liver metabolism have been described ( 14 ); for example, microbial processing of dietary fi bers, bile acids, and choline produces metabolites that regulate the activity of hepatic transcription factors and, hence, metabolic processes.Abstract The gut microbiota infl uences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fi sh oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fi sh oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fi sh oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fi sh oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition. -Caesar, R., H. Nygren, M. Orešič, and F. The composition of dietary fat is known to ...

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“…Recent works on obese rodents, mainly fed with krill oil, have shown advanced effects of n-3 PL on hepatic steatosis in comparison to n-3 PUFA bound to TG 28,29 . Additionally, Rossmeisl and others demonstrated a marked reduction in hepatic steatosis with herring-derived n-3 PL 30 . Studies on animals 31,32 and humans 33,34 have suggested that the stronger effect of n-3 PL is associated with their better bioavailability of EPA and DHA.…”

Section: Discussionmentioning

confidence: 99%

Dietary Starfish Oil Prevents Hepatic Steatosis and Hyperlipidemia in C57BL/6N Mice Fed High-fat Diet

Beppu

Yoshinaga

et al. 2017

J. Oleo Sci.

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Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice

Cited by 74 publications

References 55 publications

Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism

Dietary Starfish Oil Prevents Hepatic Steatosis and Hyperlipidemia in C57BL/6N Mice Fed High-fat Diet

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