A Comparison of the Lipid-lowering Effects of Four Different n-3 Highly Unsaturated Fatty Acids in HepG2 Cells

Nagao, Koji; Nakamitsu, Kazusa; Ishida, Hiroki; Yoshinaga, Kazuaki; Nagai, Toshiharu; Mizobe, Hoyo; Kojima, Kensuke; Yanagita, Teruyoshi; Beppu, Fumiaki; Gotoh, Naohiro

doi:10.5650/jos.ess14118

Cited by 25 publications

(19 citation statements)

References 26 publications

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“…Although Nagao et al [34] demonstrated that DHA supplementation does not affect cholesterol synthesis in HepG2 cells, gas chromatography-mass spectrometry-targeted metabolomic profiling has evidenced that DHA directly inhibits the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the first rate-limiting step of cholesterol biosynthesis [35]. Liver cells not only synthesize cholesterol, but also regulate its efflux via different metabolic pathways (i.e., very low-density lipoprotein (VLDL) secretion, bile acid synthesis).…”

Section: Discussionmentioning

confidence: 99%

Evidence of a DHA Signature in the Lipidome and Metabolome of Human Hepatocytes

Ghini

Nunzio

Tenori

et al. 2017

IJMS

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Cell supplementation with bioactive molecules often causes a perturbation in the whole intracellular environment. Omics techniques can be applied for the assessment of this perturbation. In this study, the overall effect of docosahexaenoic acid (DHA) supplementation on cultured human hepatocyte lipidome and metabolome has been investigated using nuclear magnetic resonance (NMR) in combination with traditional techniques. The effect of two additional bioactives sharing with DHA the lipid-lowering effect—propionic acid (PRO) and protocatechuic acid (PCA)—has also been evaluated in the context of possible synergism. NMR analysis of the cell lipid extracts showed that DHA supplementation, alone or in combination with PCA or PRO, strongly altered the cell lipid profile. The perfect discrimination between cells receiving DHA (alone or in combination) and the other cells reinforced the idea of a global rearrangement of the lipid environment induced by DHA. Notably, gas chromatography and fluorimetric analyses confirmed the strong discrimination obtained by NMR. The DHA signature was evidenced not only in the cell lipidome, but also in the metabolome. Results reported herein indicate that NMR, combined with other techniques, represents a fundamental approach to studying the effect of bioactive supplementation, particularly in the case of molecules with a broad spectrum of mechanisms of action.

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Section: Discussionmentioning

confidence: 99%

Evidence of a DHA Signature in the Lipidome and Metabolome of Human Hepatocytes

Ghini

Nunzio

Tenori

et al. 2017

IJMS

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“…Similarly, a study using human blood samples showed that DPA was equally effective to EPA and DHA in inhibiting platelet aggregation in female subjects . Further, a recent in vitro study showed that application of LC omega‐3s, including DPA, suppressed the synthesis of triglycerides and cholesterol in liver cells , which may explain data from epidemiological trials that linked DPA to better health outcomes.…”

Section: Biological Functions Of Dpamentioning

confidence: 95%

Dietary sources, current intakes, and nutritional role of omega‐3 docosapentaenoic acid

2015

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Fish oils and long-chain omega-3 fatty acids are well recognized for their critical role in human diets. Docosapentaenoic acid (DPA, 22 : 5n-3) has always been a part of healthy nutrition, since infants obtain almost as much DPA as DHA from human milk. Fish oil supplements and ingredients, oily fish, and grass-fed beef can serve as the primary DPA sources for the general population. Although the DPA levels in fish oils are substantially lower than those of EPA and DHA, concentrated DPA products are now becoming commercially available, and DPA-based drugs are under development.Epidemiological studies show that similar to eicosapentaenoic (EPA, 20 : 5n-3) and docosahexaenoic (DHA, 22 : 6n-3) acids, DPA is linked to various improvements in human health, perhaps owing to its structural similarity to the other two molecules. Studies in mammals, platelets, and cell cultures have demonstrated that DPA reduces platelet aggregation, and improves lipid metabolism, endothelial cell migration, and resolution of chronic inflammation. Further, other in vivo and in vitro studies have shown that DPA can improve neural health. A human supplementation trial with 99.8% pure DPA suggested that it serves as a storage depot for EPA and DHA in the human body. Future randomized controlled human trials with purified DPA will help clarify its effects on human health. They may confirm the available evidence pointing to its nutritional and biological functions, unique or overlapping with those of EPA and DHA.

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“…Although the hypolipidemic effect of omega3-PUFAs is believed to be due mostly to their potent enhancement of lipolysis through PPARa activation, it has been also reported that omega3-PUFAs inhibit hepatic lipogenesis by suppressing genes involved in fatty acid biosynthesis through the down-regulation of SREBP1c (1,4). Our recent study demonstrated that the order of inhibitory effects of omega3-PUFAs on hepatic lipogenesis was thought to be tetracosahexaenoic acid (THA, 24:6).docosahexaenoic acid (DHA, 22:6).docosapentaenoic acid (DPA, 22:5).eicosapentaenoic acid (EPA, 20:5) in HepG2 cells (5). Accompanied by our previous study showing that hepatic lipid accumulation in obese mice was strongly suppressed by omega3-PUFAs and the order of the ability was DHA .…”

Section: Effects Of Functional Lipids On Hepatic Lipid Metabolism In mentioning

confidence: 99%