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13 pages, 613 KiB

Open AccessFeature PaperArticle

Potential Beneficial Effects of Extra Virgin Olive Oils Characterized by High Content in Minor Polar Compounds in Nephropathic Patients: A Pilot Study

by Annalisa Romani, Roberta Bernini, Annalisa Noce, Silvia Urciuoli, Manuela Di Lauro, Anna Pietroboni Zaitseva, Giulia Marrone and Nicola Di Daniele

Molecules 2020, 25(20), 4757; https://doi.org/10.3390/molecules25204757 - 16 Oct 2020

Cited by 30 | Viewed by 3320

Abstract

Extra virgin olive oil (EVOO) is a lipid food, which constitutes a pillar of the Mediterranean diet. A high number of scientific data have demonstrated that it exerts a variety of beneficial effects on human health due to its peculiar chemical composition including [...] Read more.

Extra virgin olive oil (EVOO) is a lipid food, which constitutes a pillar of the Mediterranean diet. A high number of scientific data have demonstrated that it exerts a variety of beneficial effects on human health due to its peculiar chemical composition including fatty acids (98–99%) and other active compounds even if found in a very low percentage (1–2%). Among them, minor polar compounds (MCPs), represented mainly by phenolic compounds, are relevant for their healthy properties, as stated by the European Food Safety Authority’s (EFSA) claims. In this paper, we described the results obtained from a pilot in vivo study, focused for the first time on the evaluation of the possible beneficial effects of two EVOOs on chronic kidney disease (CKD) patients after the consumption of 40 mL per day for 9 weeks. The selected EVOOs, traced in the production chain, and characterized by High-Performance Liquid Chromatography (HPLC-DAD-MS) analysis, resulted rich in MCPs and satisfied the EFSA’s claim for their content of hydroxytyrosol and derivatives. The results obtained by this in vivo study appear to highlight the potential beneficial role in CKD patients of these EVOOs and are promising for future studies. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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12 pages, 826 KiB

Open AccessArticle

Polyunsaturated Fatty Acids of Both the Omega-3 and the Omega-6 Family Abrogate the Cytokine-Induced Upregulation of miR-29a-3p by Endothelial Cells

by Daniel Maucher, Birte Schmidt, Kevin Kuhlmann and Julia Schumann

Molecules 2020, 25(19), 4466; https://doi.org/10.3390/molecules25194466 - 29 Sep 2020

Cited by 9 | Viewed by 2691

Abstract

Cellular processes fundamentally depend on protein expression control. At this, protein expression is regulated on the transcriptional and the post-transcriptional level. PUFAs are already known to affect gene transcription. The present study was conducted to answer the question whether PUFAs are also able [...] Read more.

Cellular processes fundamentally depend on protein expression control. At this, protein expression is regulated on the transcriptional and the post-transcriptional level. PUFAs are already known to affect gene transcription. The present study was conducted to answer the question whether PUFAs are also able to impact on the miRNA-mediated post-transcriptional fine-tuning of mRNA copy numbers. To this end, cellular miRNA profiles were screened by means of next-generation sequencing and NanoString analysis to compare PUFA-enriched to unsupplemented endothelial cells exposed to an inflammatory milieu. Validation took place by droplet digital PCR, allowing for an absolute quantification of RNA copy numbers. The analyses revealed that the stimulation-induced upregulation of miR-29a-3p is blocked by PUFA enrichment of endothelial cells. What is more, mRNA copy numbers of miR-29a-3p targets, namely the coagulation factors PAI-1, TF, and vWF, as well as the proinflammatory cytokines IL-1β, IL-6, and IL-8, were reduced in PUFA-enriched endothelial cells compared to unsupplemented cells, counteracting the stimulatory effect of an inflammatory environment. These data hint toward a new mechanism of action by which PUFAs modulate the functionality of endothelial cells. Apparently, the inflammation-modulating properties of PUFAs are also mediated at the post-transcriptional level. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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12 pages, 2331 KiB

Open AccessCommunication

Distinct Influence of Hypercaloric Diets Predominant with Fat or Fat and Sucrose on Adipose Tissue and Liver Inflammation in Mice

by Caíque S. M. Fonseca, Joshua E. Basford, David G. Kuhel, Eddy S. Konaniah, James G. Cash, Vera L. M. Lima and David Y. Hui

Molecules 2020, 25(19), 4369; https://doi.org/10.3390/molecules25194369 - 23 Sep 2020

Cited by 5 | Viewed by 2785

Abstract

Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This [...] Read more.

Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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18 pages, 1286 KiB

Open AccessArticle

Lipid Profile Modulates Cardiometabolic Risk Biomarkers Including Hypertension in People with Type-2 Diabetes: A Focus on Unbalanced Ratio of Plasma Polyunsaturated/Saturated Fatty Acids

by Ines Gouaref, Asma Bouazza, Samir Ait Abderrhmane and Elhadj-Ahmed Koceir

Molecules 2020, 25(18), 4315; https://doi.org/10.3390/molecules25184315 - 20 Sep 2020

Cited by 11 | Viewed by 4028

Abstract

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) [...] Read more.

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio is a likely contributor, but the mechanisms involved are not clearly elucidated. The aim of this study is to explore the association between plasma SFA/PUFA ratio and the clusters of cardiometabolic syndrome (CMS), including the atherogenic biomarkers, inflammatory status, feeding patterns, and physical activity in people with T2DM with or without essential hypertension. The study was conducted on 784 adult male and female participants, aged between 30 and 50 years, and divided into 3 groups: 100 T2DM without hypertension (D); 368 T2DM with hypertension (DM); and 316 hypertensive participants without T2DM (H). All Participants were phenotyped regarding CMS clusters according to the NCEP/ATPIII criteria. Insulin resistance was assessed by Homeostasis model assessment (HOMA model). Metabolic, atherogenic, and inflammatory parameters were analyzed by biochemical methods; NEFFA by microfluorimetry; SFA, PUFA-n6 and PUFA-n3 by gas phase chromatography. Dietary lipids and physical activity were analyzed through the use of validated questionnaires. The clusters of CMS were found in all groups. Dyslipidemia was correlated with accretion NEFFA levels in all groups, but more accentuated in the DH group (r = +0.77; p < 0.001). Similarly, plasma PUFA/SFA ratio and PUFA-3 level was lower, concomitantly with a higher plasma ApoB₁₀₀/ApoA₁ (p < 0.001), lipoprotein (a), homocysteine (p < 0.001), and pro-inflammatory cytokines (TNFα, IL-6, IL1-β) in the DH group. Likewise, the depletion of PUFA-n3/PUFA-n6 ratio is associated with the decrease of omega 3-DHA (docosahexaenoic acid) and omega 3-EPA (eicosapentaenoic acid) (p < 0.001). It appears that the PUFAs-n3 ratio modulates cardiometabolic risk, inflammatory state and atherogenic biomarkers. The plasma unbalanced ratio of SFA/PUFA reflects dietary fatty acids intake. The contribution of dietary lipids is undisputed. Nutritional recommendations are required to determine the fatty acids ratio (saturated and unsaturated) provided in the diet. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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19 pages, 4614 KiB

Open AccessArticle

LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells

by Chiao-Wei Lin, Yu-Ju Peng, Yuan-Yu Lin, Harry John Mersmann and Shih-Torng Ding

Molecules 2020, 25(18), 4122; https://doi.org/10.3390/molecules25184122 - 9 Sep 2020

Cited by 14 | Viewed by 4560

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is involved in lipid metabolism; however, the role of LRRK2 in lipid metabolism to affect non-alcoholic fatty liver disease (NAFLD) is still unclear. In the mouse model of NAFLD induced by a high-fat diet, we observed that LRRK2 [...] Read more.

Leucine-rich repeat kinase 2 (LRRK2) is involved in lipid metabolism; however, the role of LRRK2 in lipid metabolism to affect non-alcoholic fatty liver disease (NAFLD) is still unclear. In the mouse model of NAFLD induced by a high-fat diet, we observed that LRRK2 was decreased in livers. In HepG2 cells, exposure to palmitic acid (PA) down-regulated LRRK2. Overexpression and knockdown of LRRK2 in HepG2 cells were performed to further investigate the roles of LRRK2 in lipid metabolism. Our results showed that β-oxidation in HepG2 cells was promoted by LRRK2 overexpression, whereas LRRK2 knockdown inhibited β-oxidation. The critical enzyme of β-oxidation, carnitine palmitoyltransferase 1A (CPT1A), was positively regulated by LRRK2. Our data suggested that the regulation of CPT1A by LRRK2 may be via the activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). The overexpression of LRRK2 reduced the concentration of a pro-inflammatory cytokine, tumor necrosis factor α (TNFα), induced by PA. The increase in β-oxidation may promote lipid catabolism to suppress inflammation induced by PA. These results indicated that LRRK2 participated in the regulation of β-oxidation and suggested that the decreased LRRK2 may promote inflammation by suppressing β-oxidation in the liver. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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11 pages, 1521 KiB

Open AccessArticle

Daurichromenic Acid from the Chinese Traditional Medicinal Plant Rhododendron dauricum Inhibits Sphingomyelin Synthase and Aβ Aggregation

by Hadya Virupaksha Deepak, Mahadeva M. M. Swamy, Yuta Murai, Yoshiko Suga, Masaki Anetai, Takuro Yo, Masahiro Kuragano, Koji Uwai, Kiyotaka Tokuraku and Kenji Monde

Molecules 2020, 25(18), 4077; https://doi.org/10.3390/molecules25184077 - 7 Sep 2020

Cited by 11 | Viewed by 4045

Abstract

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, [...] Read more.

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC₅₀ of 4 µM. The structure–activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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12 pages, 1369 KiB

Open AccessArticle

LC–MS-Based Lipidomic Analysis of Serum Samples from Spontaneously Hypertensive Rats Treated with an Extract of Acanthopanax sessiliflorus Fruits

by Dae Young Lee, Bo-Ram Choi, Dahye Yoon, Hyoung-Geun Kim, Min-Ho Lee, Geum-Soog Kim and Young-Seob Lee

Molecules 2020, 25(14), 3269; https://doi.org/10.3390/molecules25143269 - 17 Jul 2020

Viewed by 3262

Abstract

Recently, lipidomics has revealed that many diseases are highly associated with altered lipid metabolism, as in the case of hypertension affecting serum lipid metabolism. In this study, an LC–MS-based lipidomic approach was used to profile serum lipids in spontaneously hypertensive rats (SHRs) treated [...] Read more.

Recently, lipidomics has revealed that many diseases are highly associated with altered lipid metabolism, as in the case of hypertension affecting serum lipid metabolism. In this study, an LC–MS-based lipidomic approach was used to profile serum lipids in spontaneously hypertensive rats (SHRs) treated with an extract of Acanthopanax sessiliflorus fruits (ASF), to elucidate the serum lipid metabolism alteration by hypertension and the treatment of a drug or ASF. First, UPLC-QTOF/MS profiled a total of 208 lipids from six pooled samples of normal controls, SHR, SHR + 100 mg/kg of drug, and SHR + ASF 200, 400, or 600 mg/kg. These six groups were differentiated by the PCA and sPLS–DA, and 120 lipid species were identified as differentially regulated lipids (DRLs) by ANOVA (p values < 0.05). Second, UPLC–QqQ/MS was used for the target profiling of 120 DRLs from individual samples of the six groups. Using an ANOVA, 67 lipids (38 TGs, 4 DGs, 17 PCs, 2 PEs, and 6 LPCs) were selected as validated DRLs. The mostly altered lipids, such as TG (62:13), TG (60:13), PC (34:4), PC (36:5), and PC (38:2), were decreased in SHR compared to the normal control, and received little by treatment with ASF. These results demonstrated the correlation between hypertension and serum lipid metabolism. Furthermore, both drug and ASF treatment similarly altered the lipid profiles of SHRs. Finally, we found that DRLs have the potential to help us to interpret the lipid metabolism of hypertension. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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11 pages, 1139 KiB

Open AccessArticle

Characterization of Fatty Acid Composition Underlying Hypothalamic Inflammation in Aged Mice

by Ye Jin Kim, Thai Hien Tu, Sunggu Yang, Jae Kwang Kim and Jae Geun Kim

Molecules 2020, 25(14), 3170; https://doi.org/10.3390/molecules25143170 - 11 Jul 2020

Cited by 7 | Viewed by 2617

Abstract

Degenerative diseases, which can develop during aging, are underlined by inflammatory processes. Hypothalamic inflammation triggered by elevation in circulating fatty acid levels is directly coupled to metabolic disorders. The present study aimed to investigate and characterize the hypothalamic inflammation and composition of fatty [...] Read more.

Degenerative diseases, which can develop during aging, are underlined by inflammatory processes. Hypothalamic inflammation triggered by elevation in circulating fatty acid levels is directly coupled to metabolic disorders. The present study aimed to investigate and characterize the hypothalamic inflammation and composition of fatty acids in the hypothalami of aged mice. We verified that inflammation and microglial activation occur in the hypothalami of aged mice by performing quantitative real-time PCR and using immunohistochemistry methods. In addition, we observed increased levels of various saturated fatty acids in the hypothalami of aged mice, whereas no major changes in the levels of circulating fatty acids were detected using gas chromatography with a flame ionization detector. Collectively, our current findings suggest that increases in saturated fatty acid levels are coupled to hypothalamic inflammation and thereby cause perturbations in energy metabolism during the aging process. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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18 pages, 3057 KiB

Open AccessArticle

Relationship between Fatty Acids Composition/Antioxidant Potential of Breast Milk and Maternal Diet: Comparison with Infant Formulas

by Michela Codini, Carmela Tringaniello, Lina Cossignani, Antonio Boccuto, Alessandra Mirarchi, Laura Cerquiglini, Stefania Troiani, Giuseppa Verducci, Federica Filomena Patria, Carmela Conte, Samuela Cataldi, Maria Rachele Ceccarini, Rita Paroni, Michele Dei Cas, Tommaso Beccari, Francesco Curcio and Elisabetta Albi

Molecules 2020, 25(12), 2910; https://doi.org/10.3390/molecules25122910 - 24 Jun 2020

Cited by 12 | Viewed by 4020

Abstract

The fatty acid composition of human breast milk is relevant for the energy, immunity and eicosanoid production in infants. Additionally, the antioxidant properties of foods are essential for human health. Therefore, in the present study we aimed to investigate the relationship between maternal [...] Read more.

The fatty acid composition of human breast milk is relevant for the energy, immunity and eicosanoid production in infants. Additionally, the antioxidant properties of foods are essential for human health. Therefore, in the present study we aimed to investigate the relationship between maternal diet and fatty acids composition as well as the antioxidant potential of breast milk from donors to human milk bank of Perugia’s hospital, Italy. Results were compared with infant formulas. We observed increased levels of total fatty acids and, in particular, saturated and monounsaturated fatty acids in milk from mothers fed on a vegetable and fruit-rich diet compared with a Mediterranean diet. In the same milk, a reduced antioxidant potential was found. All infant formulas resulted in richer total fatty acid content than human breast milk. Only some formulas were qualitatively similar to breast milk. Of note, the antioxidant potential of the formulas was higher or lower than the human milk with the exception of one sample. The antioxidant potential of four formulas was very high. Dietary supplementation with antioxidants has been shown to have a teratogenic effect and to increase the formation of metastases in adult. There are no data on the effects of excess antioxidants in the infants, but the possibility that they can be harmful cannot be excluded. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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12 pages, 2193 KiB

Open AccessArticle

Effect of Palmitic Acid on Exosome-Mediated Secretion and Invasive Motility in Prostate Cancer Cells

by Ivan V. Maly and Wilma A. Hofmann

Molecules 2020, 25(12), 2722; https://doi.org/10.3390/molecules25122722 - 12 Jun 2020

Cited by 11 | Viewed by 3852

Abstract

High fat consumption can enhance metastasis and decrease survival in prostate cancer, but the picture remains incomplete on the epidemiological and cell-biological level, impeding progress toward individualized recommendations in the clinic. Recent work has highlighted the role of exosomes secreted by prostate cancer [...] Read more.

High fat consumption can enhance metastasis and decrease survival in prostate cancer, but the picture remains incomplete on the epidemiological and cell-biological level, impeding progress toward individualized recommendations in the clinic. Recent work has highlighted the role of exosomes secreted by prostate cancer cells in the progression of the disease, particularly in metastatic invasion, and also the utility of targeting these extracellular vesicles for diagnostics, as carriers of disease progression markers. Here, we investigated the question of a potential impact of the chief nutritional saturated fatty acid on the exosome secretion. Palmitic acid decreased the secretion of exosomes in human prostate cancer cells in vitro in a concentration-dependent manner. At the same time, the content of some prospective metastatic markers in the secreted exosomal fraction was also reduced, as was the ability of the cells to invade across extracellular matrix barriers. While by themselves our in vitro results imply that on the cell level, palmitic acid may be beneficial vis-à-vis the course of the disease, they also suggest that, by virtue of the decreased biomarker secretion, palmitic acid has the potential to cause unjustified deprioritization of treatment in obese and lipidemic men. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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10 pages, 1161 KiB

Open AccessArticle

Extra Virgin Olive Oil Phenols Dilate the Rat Mesenteric Artery by Activation of BK_Ca2+ Channels in Smooth Muscle Cells

by Rossana D’Agostino, Laura Barberio, MariaCarmela Gatto, Innocenzo Muzzalupo and Maurizio Mandalà

Molecules 2020, 25(11), 2601; https://doi.org/10.3390/molecules25112601 - 3 Jun 2020

Cited by 6 | Viewed by 2866

Abstract

Accumulating evidence has shown the beneficial health effects of extra virgin olive oil (EVOO) consumption in reducing blood pressure and preventing the risk of developing hypertension. Some studies associate the hypotensive activity of EVOO to a minor component—the phenols. This study was designed [...] Read more.

Accumulating evidence has shown the beneficial health effects of extra virgin olive oil (EVOO) consumption in reducing blood pressure and preventing the risk of developing hypertension. Some studies associate the hypotensive activity of EVOO to a minor component—the phenols. This study was designed to investigate the effects of EVOO phenols on the rat resistance mesenteric artery (MA) and to find out the possible vascular pathways involved. The experiments were carried out using a pressurized myograph, which allowed the effects of phenols on isolated MA to be tested under different conditions: (a) with endothelium removed; (b) with inhibition of nitric oxide synthase by N_ω-Nitro-l-arginine methyl ester hydrochloride (l-NAME, 10⁻⁴ M) + N_ω-Nitro-l-arginine (l-NNA, 10⁻⁴ M); (c) with inhibition of cyclooxygenase by indomethacin (10⁻⁵ M); (d) with inhibition of guanylate cyclase by 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,10⁻⁵ M) or adenylate cyclase by 9-(Tetrahydro-2′-furyl)adenine (SQ, 10⁻⁵ M); (e) with depolarization by high potassium chloride (40 mM); and (f) with inhibition of the large conductance Ca²⁺–potassium channels (BK_Ca2+) with paxilline (10⁻⁵ M). EVOO phenols induce vasodilation of the endothelium, mediated by a direct effect on smooth muscle cells (SMC) by activation of BK_Ca2+ channels, an action by which phenols can regulate the vascular tone of the resistance artery. Phenols can be regarded as bioactive molecules that may contribute to the antihypertensive effects of EVOO. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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9 pages, 431 KiB

Open AccessArticle

Eicosanoids in Nonalcoholic Fatty Liver Disease (NAFLD) Progression. Do Serum Eicosanoids Profile Correspond with Liver Eicosanoids Content during NAFLD Development and Progression?

by Dominika Maciejewska, Arleta Drozd, Karolina Skonieczna-Żydecka, Marta Skórka-Majewicz, Karolina Dec, Karolina Jakubczyk, Anna Pilutin and Ewa Stachowska

Molecules 2020, 25(9), 2026; https://doi.org/10.3390/molecules25092026 - 27 Apr 2020

Cited by 18 | Viewed by 3805

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming a major public health problem worldwide. The study aimed to evaluate the concentration of eicosanoids in serum and liver tissue during steatosis progression and to assess whether eicosanoid change scores may predict liver tissue remodeling. Thirty [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is becoming a major public health problem worldwide. The study aimed to evaluate the concentration of eicosanoids in serum and liver tissue during steatosis progression and to assess whether eicosanoid change scores may predict liver tissue remodeling. Thirty six eight-week-old male Sprague Dawley rats were enrolled and sacrificed at different stages of NAFLD. Eicosanoid concentrations, namely lipoxin A₄, hydroxyeicosatetraenoic acids (HETE), hydroxyloctadecadienoic acids (HODE), protectin DX, Maresine1, leucotriene B₄, prostaglandin E₂, and resolvin D₁ measurement in serum and liver tissue with Agilent Technologies 1260 liquid chromatography were evaluated. For the liver and serum concentrations of 9-HODE and 13-HODE, the correlations were found to be strong and positive (r > 0.7, p < 0.05). Along with NAFLD progression, HODE concentration significantly increased, and change scores were more abundant in the liver. The moderate positive correlation between liver and serum (r = 0.52, p < 0.05) was also observed for resolvin E1. The eicosanoid concentration decreased during NAFLD progression, but mostly in serum. There were significant correlations between HETE concentrations in liver and serum, but their associations were relatively low and changes the most in liver tissue. Eicosanoids profile, predominantly 9-HODE and 13-HODE, may serve as a potential biomarker for NAFLD development. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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15 pages, 846 KiB

Open AccessFeature PaperArticle

by Matina Kouvari, Demosthenes B. Panagiotakos, Christina Chrysohoou, Ekavi N. Georgousopoulou, Dimitrios Tousoulis and Christos Pitsavos

Molecules 2020, 25(7), 1506; https://doi.org/10.3390/molecules25071506 - 26 Mar 2020

Cited by 9 | Viewed by 3465

Abstract

The sex-specific effect of lipid-related biomarkers on 10-year first fatal/non fatal cardiovascular disease (CVD) incidence was evaluated. ATTICA study was conducted during 2001–2012. n = 1514 men and n = 1528 women (>18 years) from greater Athens area, Greece were recruited. Follow-up (2011–2012) [...] Read more.

The sex-specific effect of lipid-related biomarkers on 10-year first fatal/non fatal cardiovascular disease (CVD) incidence was evaluated. ATTICA study was conducted during 2001–2012. n = 1514 men and n = 1528 women (>18 years) from greater Athens area, Greece were recruited. Follow-up (2011–2012) was achieved in n = 2020 participants. Baseline lipid profile was measured. Overall CVD event was 15.5% (n = 317) (19.7% in men and 11.7% in women, p < 0.001). High density lipoprotein cholesterol (HDL-C) and triglycerides (TAG) were independently associated with CVD in women; per 10 mg/dL HDL-C increase, hazard ratio (HR) = 0.73, 95% confidence interval (95% CI) (0.53, 1.00); and per 10 mg/dL TAG increase, HR = 1.10, 95% CI (1.00, 1.21). Apolipoprotein A1 (ApoA1) (per 10 mg/dL increase, HR = 0.90, 95% CI (0.81, 0.99)) was inversely associated with CVD in women, while a positive association with apolipoprotein B100 (ApoB100) was observed only in men (per 10 mg/dL increase, HR = 1.10, 95% CI (1.00, 1.21)). Non-HDL-C was associated with CVD in the total sample (HR = 1.10, 95% CI (1.00, 1.21)) and in women (HR = 1.10, 95% CI (1.00, 1.21)); a steep increase in HR was observed for values >185 mg/dL in the total sample and in men, while in women, a raise in CVD risk was observed from lower values (>145 mg/dL). As for non-HDL-C/HDL-C and TC/HDL-C ratios, similar trends were observed. Beyond the common cholesterol-adjusted risk scores, reclassifying total CVD risk according to other lipid markers may contribute to early CVD prevention. Biomarkers such as HDL-C, non-HDL-C, and TAG should be more closely monitored in women. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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14 pages, 2683 KiB

Open AccessArticle

Simvastatin Attenuates H₂O₂-Induced Endothelial Cell Dysfunction by Reducing Endoplasmic Reticulum Stress

by Zhiqiang He, Xuanhong He, Menghan Liu, Lingyue Hua, Tian Wang, Qian Liu, Lai Chen and Nianlong Yan

Molecules 2019, 24(9), 1782; https://doi.org/10.3390/molecules24091782 - 8 May 2019

Cited by 7 | Viewed by 3721

Abstract

Atherosclerosis is the pathological basis of cardiovascular disease, whilst endothelial dysfunction (ED) plays a primary role in the occurrence and development of atherosclerosis. Simvastatin has been shown to possess significant anti-atherosclerosis activity. In this study, we evaluated the protective effect of simvastatin on [...] Read more.

Atherosclerosis is the pathological basis of cardiovascular disease, whilst endothelial dysfunction (ED) plays a primary role in the occurrence and development of atherosclerosis. Simvastatin has been shown to possess significant anti-atherosclerosis activity. In this study, we evaluated the protective effect of simvastatin on endothelial cells under oxidative stress and elucidated its underlying mechanisms. Simvastatin was found to attenuate H₂O₂-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/β-catenin pathway; however, when this pathway was activated by lithium chloride, endothelial dysfunction was clearly enhanced. Further investigation revealed that simvastatin did not alter the expression or phosphorylation of LRP6, but reduced intracellular cholesterol deposition and inhibited endoplasmic reticulum (ER) stress. Inducing ER stress with tunicamycin activated the Wnt/β-catenin pathway, whereas reducing ER stress with 4-phenylbutyric acid inhibited it. We hypothesize that simvastatin does not affect transmembrane signal transduction in the Wnt/β-catenin pathway, but inhibits ER stress by reducing intracellular cholesterol accumulation, which blocks intracellular signal transduction in the Wnt/β-catenin pathway and ameliorates endothelial dysfunction. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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Review

Jump to: Research

22 pages, 1146 KiB

Open AccessReview

The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates

by Jocelijn Meijerink

Molecules 2021, 26(5), 1416; https://doi.org/10.3390/molecules26051416 - 5 Mar 2021

Cited by 14 | Viewed by 5639

Abstract

Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free [...] Read more.

Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free fatty acids receptors (FFARs). This review focusses on two more recently emerging research lines: the roles of odorant receptors (ORs), and those of fatty acid conjugates in gut. Odorant receptors belong to a large family of GPCRs with functional roles that only lately have shown to reach beyond the nasal-oral cavity. In the intestinal tract, ORs are expressed on serotonin (5-HT) and glucagon-like-peptide-1 (GLP-1) producing enterochromaffin and enteroendocrine L cells, respectively. There, they appear to function as chemosensors of microbiologically produced short-, and branched-chain fatty acids. Another mechanism of fatty acid signaling in the intestine occurs via their conjugates. Among them, conjugates of unsaturated long chain fatty acids and acetate with 5-HT, N-acyl serotonins have recently emerged as mediators with immune-modulatory effects. In this review, novel findings in mechanisms and molecular players involved in intestinal fatty acid biology are highlighted and their potential relevance for EEC-mediated signaling to the pancreas, immune system, and brain is discussed. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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14 pages, 250 KiB

Open AccessReview

High-Sensitivity C-Reactive Protein and Carotid Intima Media Thickness as Markers of Subclinical Inflammation and Atherosclerosis in Pediatric Patients with Hypercholesterolemia

by Lana Blinc, Matej Mlinaric, Tadej Battelino and Urh Groselj

Molecules 2020, 25(21), 5118; https://doi.org/10.3390/molecules25215118 - 4 Nov 2020

Cited by 11 | Viewed by 3214

Abstract

Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in [...] Read more.

Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in one of the causative genes (LDLR, APOB, PCSK9). In polygenic hypercholesterolemia (PH), the disease-causing genetic variant is absent; it is likely the cumulative result of multiple single nucleotide polymorphisms in LDL metabolism-related genes and other factors, such as lifestyle and environment. In high risk groups, such as patients with FH, an effective primary prevention of CVD must begin in childhood. High-sensitivity C-reactive protein (hsCRP) and carotid intima media thickness (cIMT) are two potential minimally invasive correlates of inflammation and subclinical atherosclerosis progression. hsCRP and cIMT have been shown to be significantly increased in patients with FH and PH relative to healthy controls, with some studies yielding conflicting results. In this review, we aim to summarize current knowledge and recent findings regarding the applicability of hsCRP and cIMT as markers of low-grade inflammation and subclinical atherosclerosis, focusing especially on children and adolescents with hypercholesterolemia. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

33 pages, 2080 KiB

Open AccessReview

Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease

by Florian Geltinger, Lukas Schartel, Markus Wiederstein, Julia Tevini, Elmar Aigner, Thomas K. Felder and Mark Rinnerthaler

Molecules 2020, 25(21), 5053; https://doi.org/10.3390/molecules25215053 - 30 Oct 2020

Cited by 48 | Viewed by 10303

Abstract

Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular [...] Read more.

Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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19 pages, 1392 KiB

Open AccessReview

The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer

by Rui Guo, Yu Chen, Heather Borgard, Mayumi Jijiwa, Masaki Nasu, Min He and Youping Deng

Molecules 2020, 25(20), 4864; https://doi.org/10.3390/molecules25204864 - 21 Oct 2020

Cited by 42 | Viewed by 6938

Abstract

Lipids are essential components of cell structure and play important roles in signal transduction between cells and body metabolism. With the continuous development and innovation of lipidomics technology, many studies have shown that the relationship between lipids and cancer is steadily increasing, involving [...] Read more.

Lipids are essential components of cell structure and play important roles in signal transduction between cells and body metabolism. With the continuous development and innovation of lipidomics technology, many studies have shown that the relationship between lipids and cancer is steadily increasing, involving cancer occurrence, proliferation, migration, and apoptosis. Breast cancer has seriously affected the safety and quality of life of human beings worldwide and has become a significant public health problem in modern society, with an especially high incidence among women. Therefore, the issue has inspired scientific researchers to study the link between lipids and breast cancer. This article reviews the research progress of lipidomics, the biological characteristics of lipid molecules, and the relationship between some lipids and cancer drug resistance. Furthermore, this work summarizes the lipid molecules related to breast cancer diagnosis and prognosis, and then it clarifies their impact on the occurrence and development of breast cancer The discussion revolves around the current research hotspot long-chain non-coding RNAs (lncRNAs), summarizes and explains their impact on tumor lipid metabolism, and provides more scientific basis for future cancer research studies. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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21 pages, 906 KiB

Open AccessReview

The Lipidome Fingerprint of Longevity

by Mariona Jové, Natàlia Mota-Martorell, Irene Pradas, José Daniel Galo-Licona, Meritxell Martín-Gari, Èlia Obis, Joaquim Sol and Reinald Pamplona

Molecules 2020, 25(18), 4343; https://doi.org/10.3390/molecules25184343 - 22 Sep 2020

Cited by 19 | Viewed by 4682

Abstract

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that [...] Read more.

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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22 pages, 1368 KiB

Open AccessReview

Fatty Acid Synthase: An Emerging Target in Cancer

by Chee Wai Fhu and Azhar Ali

Molecules 2020, 25(17), 3935; https://doi.org/10.3390/molecules25173935 - 28 Aug 2020

Cited by 246 | Viewed by 15548

Abstract

In recent years, lipid metabolism has garnered significant attention as it provides the necessary building blocks required to sustain tumor growth and serves as an alternative fuel source for ATP generation. Fatty acid synthase (FASN) functions as a central regulator of lipid metabolism [...] Read more.

In recent years, lipid metabolism has garnered significant attention as it provides the necessary building blocks required to sustain tumor growth and serves as an alternative fuel source for ATP generation. Fatty acid synthase (FASN) functions as a central regulator of lipid metabolism and plays a critical role in the growth and survival of tumors with lipogenic phenotypes. Accumulating evidence has shown that it is capable of rewiring tumor cells for greater energy flexibility to attain their high energy requirements. This multi-enzyme protein is capable of modulating the function of subcellular organelles for optimal function under different conditions. Apart from lipid metabolism, FASN has functional roles in other cellular processes such as glycolysis and amino acid metabolism. These pivotal roles of FASN in lipid metabolism make it an attractive target in the clinic with several new inhibitors currently being tested in early clinical trials. This article aims to present the current evidence on the emergence of FASN as a target in human malignancies. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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21 pages, 5196 KiB

Open AccessReview

An Atomic-Level Perspective of HMG-CoA-Reductase: The Target Enzyme to Treat Hypercholesterolemia

by Diana S. Gesto, Carlos M. S. Pereira, Nuno M. F. S. Cerqueira and Sérgio F. Sousa

Molecules 2020, 25(17), 3891; https://doi.org/10.3390/molecules25173891 - 26 Aug 2020

Cited by 39 | Viewed by 8985

Abstract

This review provides an updated atomic-level perspective regarding the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), linking the more recent data on this enzyme with a structure/function interpretation. This enzyme catalyzes one of the most important steps in cholesterol biosynthesis and is regarded as [...] Read more.

This review provides an updated atomic-level perspective regarding the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), linking the more recent data on this enzyme with a structure/function interpretation. This enzyme catalyzes one of the most important steps in cholesterol biosynthesis and is regarded as one of the most important drug targets in the treatment of hypercholesterolemia. Taking this into consideration, we review in the present article several aspects of this enzyme, including its structure and biochemistry, its catalytic mechanism and different reported and proposed approaches for inhibiting this enzyme, including the commercially available statins or the possibility of using dimerization inhibitors. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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20 pages, 1760 KiB

Open AccessReview

Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis

by Katarzyna Bocheńska and Magdalena Gabig-Cimińska

Molecules 2020, 25(5), 1130; https://doi.org/10.3390/molecules25051130 - 3 Mar 2020

Cited by 19 | Viewed by 6831

Abstract

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), [...] Read more.

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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12 pages, 665 KiB

Open AccessFeature PaperReview

Adropin as A Fat-Burning Hormone with Multiple Functions—Review of a Decade of Research

by Mariami Jasaszwili, Maria Billert, Mathias Z. Strowski, Krzysztof W. Nowak and Marek Skrzypski

Molecules 2020, 25(3), 549; https://doi.org/10.3390/molecules25030549 - 27 Jan 2020

Cited by 75 | Viewed by 7946

Abstract

Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. [...] Read more.

Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. A decade after its discovery, there is evidence that adropin may contribute to body weight regulation, glucose and lipid homeostasis, and cardiovascular system functions. In this review, we summarize and discuss the physiological, metabolic, and pathophysiological factors regulating Enho as well as adropin. Furthermore, we review the literature addressing the role of adropin in adiposity and type 2 diabetes. Finally, we elaborate on the role of adropin in the context of the cardiovascular system, liver diseases, and cancer. Full article

(This article belongs to the Special Issue Lipids in Health and Disease)

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