Effect of Structured Phenolic Lipids with EPA/DHA and Gallic Acid against Metabolic-Associated Fatty Liver Disease (MAFLD) in Mice.

Obesity is the leading risk factor for developing metabolic (dysfunction)-associated fatty liver disease (MAFLD). The food industry has an essential role in searching for new strategies to improve primary food sources to revert some of the metabolic alterations induced by obesity. There is consistent evidence that long-chain polyunsaturated fatty acids (n-3 LCPUFA) belonging to the n-3 series, i.e., eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) acids, could revert some alterations associated with obesity-induced metabolic diseases. A relevant tool is the synthesis of structured acylglycerols (sAG), which include EPA or DHA at the sn-2 position. On the other hand, it has been reported that a crucial role of antioxidants is the reversion of MAFLD. In this work, we studied the effects of new molecules incorporating gallic acid (GA) into EPA/DHA-rich structured lipids. Mice were fed with a high-fat diet (60%) for three months and were then divided into five groups for supplementation with sAG and sAG structured with gallic acid (structured phenolic acylglycerols, sPAG). sPAG synthesis was optimized using a 2²-screening factorial design based on the response surface methodology (RSM). Our results show that treatment of sPAG was effective in decreasing visceral fat, fasting glycemia, fasting insulin, suggesting that this new molecule has a potential use in the reversal of MAFLD-associated alterations.

EPA/DHA Concentrate by Urea Complexation Decreases Hyperinsulinemia and Increases Plin5 in the Liver of Mice Fed a High-Fat Diet.

Dietary intake of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) reduces insulin resistance and hepatic manifestations through the regulation of metabolism in the liver. Obese mice present insulin resistance and lipid accumulation in intracellular lipid droplets (LDs). LD-associated proteins perilipin (Plin) have an essential role in both adipogenesis and lipolysis; Plin5 regulates lipolysis and thus contributes to fat oxidation. The purpose of this study was to compare the effects of deodorized refined salmon oil (DSO) and its polyunsaturated fatty acids concentrate (CPUFA) containing EPA and DHA, obtained by complexing with urea, on obesity-induced metabolic alteration. CPUFA maximum content was determined using the Box-Behnken experimental design based on Surface Response Methodology. The optimized CPUFA was administered to high-fat diet (HFD)-fed mice (200 mg/kg/day of EPA + DHA) for 8 weeks. No significant differences (p > 0.05) in cholesterol, glycemia, LDs or transaminase content were found. Fasting insulin and hepatic Plin5 protein level increased in the group supplemented with the EPA + DHA optimized product (38.35 g/100 g total fatty acids) compared to obese mice without fish oil supplementation. The results suggest that processing salmon oil by urea concentration can generate an EPA+DHA dose useful to prevent the increase of fasting insulin and the decrease of Plin5 in the liver of insulin-resistant mice.

Iron-induced derangement in hepatic Δ-5 and Δ-6 desaturation capacity and fatty acid profile leading to steatosis: Impact on extrahepatic tissues and prevention by antioxidant-rich extra virgin olive oil.

The administration of iron induces liver oxidative stress and depletion of long-chain polyunsaturated fatty acids (LCPUFAs), n-6/n-3 LCPUFA ratio enhancement and fat accumulation, which may be prevented by antioxidant-rich extra virgin olive oil (AR-EVOO) supplementation. Male Wistar rats were subjected to a control diet (50 mg iron/kg diet) or iron-rich diet (IRD; 200 mg/kg diet) with alternate AR-EVOO for 21 days. Liver fatty acid (FA) analysis was performed by gas-liquid chromatography (GLC) after lipid extraction and fractionation, besides Δ-5 desaturase (Δ-5 D) and Δ6-D mRNA expression (qPCR) and activity (GLC) measurements. The IRD significantly (p < 0.05) increased hepatic total fat, triacylglycerols, free FA contents and serum transaminases levels, with diminution in those of n-6 and n-3 LCPUFAs, higher n-6/n-3 ratios, lower unsaturation index and Δ5-D and Δ6-D activities, whereas the mRNA expression of both desaturases was enhanced over control values, changes that were prevented by concomitant AR-EVOO supplementation. N-6 and n-3 LCPUFAs were also decreased by IRD in extrahepatic tissues and normalized by AR-EVOO. In conclusion, AR-EVOO supplementation prevents IRD-induced changes in parameters related to liver FA metabolism and steatosis, an effect that may have a significant impact in the treatment of iron-related pathologies or metabolic disorders such as non-alcoholic fatty liver disease.

Anti-oxidative and anti-inflammatory effects of Rosa Mosqueta oil supplementation in rat liver ischemia-reperfusion.

Ischemia-reperfusion (IR) is a deleterious condition associated with liver transplantation or resection that involves pro-oxidant and pro-inflammatory mechanisms. Considering that Rosa Mosqueta (RM) oil composition is rich in protective components such as α-linolenic acid (ALA) and tocopherols, we studied the effects of RM oil supplementation given prior to an IR protocol. Male Sprague-Dawley rats receiving RM oil (0.4 mL d-1) for 21 days were subjected to 1 h of ischemia followed by 20 h reperfusion. Parameters of liver injury (serum transaminases, histology), oxidative stress [liver contents of protein carbonyls, thiobarbituric acid reactants, Nrf2 activity and its target mRNA expression of heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1)] and inflammation [nuclear factor-κB (NF-κB) and its target mRNA expression of tumor necrosis factor-α (TNF-α) and interleukine-1ß (IL-1ß)] were studied. RM oil increased liver ALA and its derived EPA and DHA fatty acids' contents, with enhancement in those of α- and γ-tocopherols. IR induced inflammatory liver injury, with enhancement in serum transaminases, oxidative stress-related parameters with reduced Nrf2 signaling, and higher pro-inflammatory cytokines, indexes that were attenuated or abrogated by RM oil pretreatment. It is concluded that RM oil supplementation represents a novel non-invasive preconditioning strategy against liver injury induced by IR that has potential clinical applications in metabolic stress conditions.

Molecular mechanisms related to the hepatoprotective effects of antioxidant-rich extra virgin olive oil supplementation in rats subjected to short-term iron administration.

Enhanced iron levels in liver are associated with oxidative stress development and damage with increased fat accumulation. The aim of this work was to assess the hypothesis that antioxidant-rich extra virgin olive oil (AR-EVOO) counteracts iron-rich diet (IRD)-induced oxidative stress hindering hepatic steatosis. Male Wistar rats were fed and IRD (200 mg iron/kg diet) versus a control diet (CD; 50 mg iron/kg diet) with alternate AR-EVOO supplementation (100 mg/day) for 21 days. IRD induced liver steatosis and oxidative stress (higher levels of protein oxidation and lipid peroxidation with glutathione depletion), mitochondrial dysfunction (decreased citrate synthase and complex I and II activities) and loss of polyunsaturated fatty acids (PUFAs), with a drastic enhancement in the sterol regulatory element-binding protein-1c (SREBP-1c)/peroxisome proliferator-activated receptor-α (PPAR-α) ratio upregulating the expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid (FA) synthase and stearoyl desaturase 2) and downregulating those involved in FA oxidation (carnitine palmitoyl transferase and acyl-CoA oxidase) over values in the CD group. IRD also upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its target genes. AR-EVOO supplementation alone did not modify the studied parameters, however, IRD combined with AR-EVOO administration returned IRD-induced changes to baseline levels of the CD group. It is concluded that IRD-induced non-alcoholic fatty liver disease (NAFLD) is prevented by AR-EVOO supplementation, which might be related to the protective effects of its components such as hydroxytyrosol, oleic acid, tocopherols and/or PUFAs, thus representing a suitable anti-steatotic strategy to avoid progression into more severe stages of the disease, underlying NAFLD associated with iron overloading pathologies or obesity.

Role of dietary α- and γ-tocopherol from Rosa mosqueta oil in the prevention of alterations induced by high-fat diet in a murine model.

OBJECTIVE: The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations. METHODS: Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM- without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 ß expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated. RESULTS: Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM- compared with the HFD + RM, with no differences between HFD and HFD + RM-. CONCLUSION: The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.

Supplementation with Docosahexaenoic Acid and Extra Virgin Olive Oil Prevents Liver Steatosis Induced by a High-Fat Diet in Mice through PPAR-α and Nrf2 Upregulation with Concomitant SREBP-1c and NF-kB Downregulation.

SCOPE: Nonalcoholic fatty liver disease is the most common cause of liver disease, for which there is no validated drug therapy at present time. In this respect, the PUFA docosahexaenoic acid (DHA; C22:6 n-3) modulate lipid metabolism in the liver, and extra virgin olive oil (EVOO) has hepatoprotective effects. METHODS AND RESULTS: The effect of combined DHA (C22:6 n-3) and EVOO administration to mice on oxidative stress and metabolic disturbances induced by high-fat diet (HFD) is evaluated. Male C57BL/6J mice are fed with a control diet (10% fat, 20% protein, and 70% carbohydrates) or an HFD (60% fat, 20% protein, and 20% carbohydrates) for 12 weeks. Animals are supplemented with DHA (50 mg/kg/day), EVOO (50 mg/kg/day), or DHA + EVOO through oral route. DHA + EVOO cosupplementation results in greater protection (p < 0.05) over that elicited by DHA or EVOO supply alone, when compared to the damage induced by HFD. DHA + EVOO significantly reduces hepatic steatosis, oxidative stress, systemic inflammation, and insulin resistance. CONCLUSION: Synergistic beneficial effects of DHA + EVOO supplementation are associated with the activation/inactivation of key transcription factors involved in the above-mentioned processes. Data presented indicate that dietary supplementation with DHA + EVOO drastically reduces the development of nonalcoholic fatty liver disease.

Supplementation with antioxidant-rich extra virgin olive oil prevents hepatic oxidative stress and reduction of desaturation capacity in mice fed a high-fat diet: Effects on fatty acid composition in liver and extrahepatic tissues.

OBJECTIVE: The aim of this study was to assess the effect of dietary supplementation with extra virgin olive oil (EVOO) in mice on the reduction of desaturase and antioxidant enzymatic activities in liver, concomitantly with long-chain polyunsaturated fatty acids (LCPUFA) profiles in liver and extrahepatic tissues induced by a high-fat diet (HFD). METHODS: Male mice C57 BL/6 J were fed with a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or an HFD (60% fat, 20% protein, 20% carbohydrates) for 12 wk. Animals were supplemented with 100 mg/d EVOO with different antioxidant contents (EVOO I, II, and III). RESULTS: After the intervention, blood and several tissues were analyzed. Dietary supplementation with EVOO with the highest antioxidant content and antioxidant capacity (EVOO III) significantly reduced fat accumulation in liver and the plasmatic metabolic alterations caused by HFD and produced a normalization of oxidative stress-related parameters, desaturase activities, and LCPUFA content in tissues. CONCLUSIONS: Data suggest that dietary supplementation with EVOO III may prevent oxidative stress and reduction of biosynthesis and accretion of ω-3 LCPUFA in the liver of HFD-fed mice.

Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is characterized by liver steatosis, oxidative stress, and drastic depletion of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), namely, eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA), which trigger lipolysis stimulation and lipogenesis inhibition. Extra virgin olive oil (EVOO) has important antioxidant effects. This study evaluated the anti-steatotic effects of n-3 LCPUFA plus EVOO in the liver of male C57BL/6J mice subjected to a control diet (CD) (10% fat, 20% protein, 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, 20% carbohydrate), without and with supplementation with n-3 LCPUFA (100 mg per kg per day) plus EVOO (100 mg per kg per day) for 12 weeks. HFD induced (i) liver steatosis (increased total fat, triacylglycerols, and free fatty acid total contents), (ii) higher fasting serum glucose and insulin levels and HOMA index, total cholesterol, triacylglycerols and TNF-α and IL-6, (iii) liver and plasma oxidative stress enhancement, (iv) depletion of the n-3 LCPUFA hepatic content, and (v) increment in lipogenic enzyme activity and reduction in lipolytic enzyme activity. These changes were either reduced (p < 0.05) or normalized to control the values in animals subjected to HFD supplemented with n-3 LCPUFA plus EVOO. In conclusion, n-3 LCPUFA plus EVOO intervention exerts anti-steatotic effects underlying antioxidant and anti-inflammatory responses, improved insulin sensitivity, and recovery of the lipolytic/lipogenic status of the liver altered by HFD, and supports the potential therapeutic use of n-3 LCPUFA plus EVOO supplementation in the treatment of human liver steatosis induced by nutritional factors or other etiologies.

Comparative study of virgin olive oil quality from single varieties cultivated in Chile and Spain.

Olive tree varieties that were cultivated only in the Mediterranean basin a few decades ago are now planted in the Southern Hemisphere as well. The chemical composition of the oils produced in countries as far distant as Spain and Chile are affected by differences in latitude and climate. In this work, seven monovarietal virgin olive oils from Chile (Arbequina, Barnea, Frantoio, Koroneiki, Leccino, Manzanilla and Picual) have been characterized by the chemical compounds responsible for taste (phenols) and aroma (volatiles). The oils were produced in five regions of Chile, and the concentration values of some chemical compounds were related to the geographical location of the olive tree orchards. Virgin olive oils from the major cultivars, Arbequina and Picual, were characterized in comparison with the same monovarietal oils produced in Spain. The concentration values of fourteen volatile compounds showed significant differences (p < 0.05) between the oils produced in Spain and Chile. Concerning the phenol composition, main differences were found on the secoiridoids derivatives of oleuropein and ligstroside, apigenin and luteolin.

Contenido y calidad de los lípidos extraídos de raciones alimenticias de consumo habitual en Chile: (2o contribución) / Fat content and quality of the lipid extract of widely consumed meals in Chile

Se estudia la cantidad y calidad de las materias grasas aportadas por cuatro raciones de consumo habitual, consistentes en un complemento de desayuno a base de huevo, cazuela de ave, chuletas de cerdo con arroz, y escalopas de vacuno con papas fritas y huevo frito. Para cada una se realizaron cuatro muestreos. Las determinaciones realizadas fueron las siguientes: peso neto, humedad, contenido de materia grasa y composición en ácidos grasos del extracto lipídico total. De los resultados obtenidos se puede concluir que: la ración con mayor aporte calórico fue la de escalopa de vacuno con papas fritas y huevo frito con valores por ración promedio de 46,68 g y 420,12 kcal, respectivamente. La de menor aporte fue la cazuela de ave con rangos de 11,6 a 23,8 g/ración y 103,5 a 214,2 kcal/ración, respectivamente. Con respecto a la composición en ácidos grasos, las raciones de chuletas de cerdo con arroz y escalopas de vacuno, presentaron el mayor porcentaje de ácidos grasos poliinsaturados, mientras que la cazuela de ave presentó el menor aporte en estos ácidos grasos. Todas las raciones presentaron un buen aporte en ácido linoleico a excepción de la cazuela de ave. En todas las raciones analizadas se encontró ácido erúcico, en cantidades apreciables, lo que es indicativo del uso de aceite de raps (colza) con alto contenido de ácido erúcico.