Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils

Reyes-Quiróz, María Edith; Álba, Gonzalo; Sáenz, Javier; Santa-María, Consuelo; Geniz, Isabel; Jiménez, Juan; Ramı́rez, Remedios; Martı́n-Nieto, José; Pintado, Elı́zabeth; Sobrino, Francisco

doi:10.1007/s00394-014-0677-0

Cited by 29 publications

(29 citation statements)

References 47 publications

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“…3). As previously reported in human livers27282930313233, SREBP1c expression was significantly decreased in NAFL patients compared to control whereas it was increased in NASH patients compared to NAFL2 (Supplemental Fig. S5f).…”

Section: Resultssupporting

confidence: 83%

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

Chiappini¹,

Coilly²,

Kadar³

et al. 2017

Sci Rep

191

219

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Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression.

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Section: Resultssupporting

confidence: 83%

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

Chiappini¹,

Coilly²,

Kadar³

et al. 2017

Sci Rep

191

219

View full text Add to dashboard Cite

show abstract

“…It is interesting to note the antinomy existing between cholesterol and oleic acid. Indeed, we showed that oleate rich diet decreased cholesterolemia and it has also been reported that oleate increases the expression of ABCA1 , a key player involved in reverse cholesterol transport, in human neutrophils [14]. Conversely, Scd1 whole body knockout mice fed a low fat high carbohydrate diet (a model of complete oleic acid depletion) displays hypercholesterolemia and cholestasis [53].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been shown that oleic acid could modulate the activity of Liver X Receptors (LXR) in human neutrophils [14]. Moreover, LXR activity is sensitive to fatty acids in vitro [15] and it plays a central role in the hepatic effect of dietary fatty acids on lipogenesis in vivo [16].…”

Section: Introductionmentioning

confidence: 99%

Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling

et al. 2017

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Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/-) fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver.

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“…OA could stimulate mRNA synthesis of liver X‐receptor alpha (LXRα) in human neutrophils . It can also reduce intracellular lipid levels and inflammatory markers .…”

Section: Knowledge Gaps and Future Directionsmentioning

confidence: 99%

“…It can also reduce intracellular lipid levels and inflammatory markers . Conversely, OA induced hepatic steatosis through the upregulation of p38 signalling in an in vitro model . As a result, a dual effect has been suggested for OA in patients with NAFLD; therefore, future robust human clinical trials are needed in this area.…”

Section: Knowledge Gaps and Future Directionsmentioning

confidence: 99%

The effects of oleoylethanolamide, an endogenous PPAR‐α agonist, on risk factors for NAFLD: A systematic review

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease.Recently, some novel compounds have been investigated for the prevention and treatment of NAFLD. Oleoylethanolamide (OEA), an endogenous PPAR-α agonist, has exhibited a plethora of pharmacological properties for the treatment of obesity and other obesity-associated metabolic complications. This systematic review was performed with a focus on the effects of OEA on the risk factors for NAFLD.PubMed, Scopus, Embase, ProQuest, and Google Scholar databases were searched up to December 2018 using relevant keywords. All articles written in English evaluating the effects of OEA on the risk factors for NAFLD were eligible for the review. The evidence reviewed in this article illustrates that OEA regulates multiple biological processes associated with NAFLD, including lipid metabolism, inflammation, oxidative stress, and energy homeostasis through different mechanisms. In summary, many beneficial effects of OEA have led to the understanding that OEA may be an effective therapeutic strategy for the management of NAFLD. Although a wide range of studies have demonstrated the most useful effects of OEA on NAFLD and the associated risk factors, further clinical trials, from both in vivo studies and in vitro experiments, are warranted to verify these outcomes.

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Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils

Abstract: This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.

Cited by 29 publications

References 47 publications

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling

The effects of oleoylethanolamide, an endogenous PPAR‐α agonist, on risk factors for NAFLD: A systematic review

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