Dietary docosahexaenoic acid (DHA) downregulates liver DHA synthesis by inhibiting eicosapentaenoic acid elongation.

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA; 18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13C content (δ13C) of DHA via compound-specific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound-specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver-specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.

Relevant Aspects of Combined Protocols for Prevention of N(M)AFLD and Other Non-Communicable Diseases.

Obesity is a global health issue characterized by the excessive fat accumulation, leading to an increased risk of chronic noncommunicable diseases (NCDs), including metabolic dysfunction-associated fatty liver disease (MAFLD), which can progress from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, there are no approved pharmacological protocols for prevention/treatment of MAFLD, and due the complexity lying beneath these mechanisms, monotherapies are unlikely to be efficacious. This review article analyzes the possibility that NCDs can be prevented or attenuated by the combination of bioactive substances, as they could promote higher response rates, maximum reaction results, additive or synergistic effects due to compounds having similar or different mechanisms of action and/or refraining possible side effects, related to the use of lower doses and exposures times than monotherapies. Accordingly, prevention of mouse MAFLD is observed with the combination of the omega-3 docosahexaenoic acid with the antioxidant hydroxytyrosol, whereas attenuation of mild cognitive impairment is attained by folic acid plus cobalamin in elderly patients. The existence of several drawbacks underlying published monotherapies or combined trials, opens space for adequate and stricter experimental and clinical tryouts to achieve meaningful outcomes with human applicability.

High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients.

OBJECTIVE: Polyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients. METHODS: Our prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden. RESULTS: A total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855). CONCLUSIONS: Pending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2-positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.

Effect of refining and pressing temperature on chemical attributes of canola oil produced in Chile

The consumption of vegetable oils is common in our daily diet. Rapeseed oil (canola oil) is the third most consumed edible oil in the world, followed by palm and soybean oils in terms of production. Rapeseed oil has a low proportion of saturated fatty acids, while it is rich in unsaturated fatty acids, as well as in healthy compounds such as phenols, tocopherols, phytosterols, carotenoids, and fat-soluble vitamins. However, processing technologies affect the content and functional activities of bioactive compounds in the oil. Aim: To assess any potential effect of hot or cold pressing and a refining process on the nutritional value and the profile of several bioactive compounds in canola oils produced in Chile. Methods: Canola oils were characterized regarding their fatty acid profile, phytosterol and tocopherol composition, total phenol content, and antioxidant activity, according to the mode of extraction (cold or hot pressed) and before and after bWeing subjected to a refining process. Results: Fatty acid profiles were not significantly different in any of the analyzed canola oils. Refining but not temperature extraction led to a sharp decrease of phytosterols and tocopherols. Hot pressing significantly increased the amount of total phenols (3.1 times) and the antioxidant activity measured by ORAC (3.1 times) and DPPH (8.3 times) compared to the cold extraction. However, phenolic concentration and antioxidant capacity decreased after refining. Conclusions: Refining processes should be adjusted to reduce the loss of bioactive compounds in the oil.

El consumo de aceites vegetales es habitual en nuestra dieta diaria. El aceite de colza (aceite de canola) es el tercer aceite comestible más consumido en el mundo, seguido por los aceites de palma y soja en términos de producción. El aceite de colza tiene una baja proporción de ácidos grasos saturados, mientras que es rico en ácidos grasos insaturados, así como en compuestos liposolubles saludables como fenoles, tocoferoles, fitoesteroles, carotenoides y vitaminas. Sin embargo, las tecnologías de procesamiento afectan el contenido y las actividades funcionales de los compuestos bioactivos en el aceite. Objetivo: Evaluar cualquier efecto potencial del prensado en caliente o en frío y un proceso de refinación sobre el valor nutricional y el perfil de varios compuestos bioactivos en los aceites de canola producidos en Chile. Métodos: Los aceites de canola se caracterizaron en cuanto a su perfil de ácidos grasos, composición de fitoesteroles y tocoferoles, contenido de fenoles totales y actividad antioxidante, según el modo de extracción (prensado en frío o en caliente) y antes y después de ser sometidos a un proceso de refinación. Resultados: Los perfiles de ácidos grasos no fueron significativamente diferentes en ninguno de los aceites de canola analizados. La refinación, pero no la extracción en caliente, condujo a una fuerte disminución de los fitoesteroles y tocoferoles. El prensado en caliente aumentó significativamente la cantidad de fenoles totales (3,1 veces) y la actividad antioxidante medida por ORAC (3,1 veces) y DPPH (8,3 veces) en comparación con la extracción en frío. Sin embargo, la concentración de fenoles y la capacidad antioxidante disminuyeron después del refinado. Conclusión: Los procesos de refinación deben ajustarse para reducir la pérdida de compuestos bioactivos en el aceite.

Non-Infectious Uveitis and Pregnancy, is There an Optimal Treatment? Uveitis Course and Safety of Uveitis Treatment in Pregnancy.

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.

Protein concentrations and activities of fatty acid desaturase and elongase enzymes in liver, brain, testicle, and kidney from mice: Substrate dependency.

The synthesis rates of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n-3 and n-6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight-week-old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at -80°C. The protein concentration of the enzymes (Δ-6D, Δ-5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ-6D, Δ-5D, and Elovl2 have a higher affinity for n-3 PUFA precursors compared to n-6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n-3 PUFAs.

Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.

Dietary and Nutritional Interventions in Nonalcoholic Fatty Liver Disease in Pediatrics.

Nonalcoholic fatty liver disease (NAFLD) is pediatrics' most common chronic liver disease. The incidence is high in children and adolescents with obesity, which is associated with an increased risk of disease progression. Currently, there is no effective drug therapy in pediatrics; therefore, lifestyle interventions remain the first line of treatment. This review aims to present an updated compilation of the scientific evidence for treating this pathology, including lifestyle modifications, such as exercise and dietary changes, highlighting specific nutritional strategies. The bibliographic review was carried out in different databases, including studies within the pediatric population where dietary and/or nutritional interventions were used to treat NAFLD. Main interventions include diets low in carbohydrates, free sugars, fructose, and lipids, in addition to healthy eating patterns and possible nutritional interventions with n-3 polyunsaturated fatty acids (EPA and DHA), amino acids (cysteine, L-carnitine), cysteamine, vitamins, and probiotics (one strain or multi-strain). Lifestyle changes remain the main recommendation for children with NAFLD. Nevertheless, more studies are required to elucidate the effectiveness of specific nutrients and bioactive compounds in this population.

Dietary triacetin, but not medium chain triacylglycerides, blunts weight gain in diet-induced rat model of obesity.

Consumption of a Western diet (WD) is known to increase the risk of obesity. Short or medium chain fatty acids influence energy metabolism, and triacetin, a synthetic short chain triacylglyceride, has been shown to lower body fat under normal conditions. This study aimed to investigate if triacetin as part of a WD modifies rat weight and body fat. Male rats were fed a control diet or WD for 8 weeks. At week 8, rats in the WD group were maintained on a WD diet or switched to a WD diet containing 30% energy from medium-chain triacylglyceride (WD-MCT) or triacetin (WD-T) for another 8 weeks. At week 16, rats were euthanized and liver, adipose and blood were collected. Tissue fatty acids (FAs) were quantified by gas chromatography (GC) and hepatic FAs were measured by GC-combustion-isotope ratio mass spectrometry for δ13 C-palmitic acid (PAM)-a novel marker of de novo lipogenesis (DNL). Rats fed WD-T had a body weight not statistically different to the control group, and gained less body weight than rats fed WD alone. Furthermore, WD-T fed rats had a lower fat mass, and lower total liver and plasma FAs compared to the WD group. Rats fed WD-T did not differ from WD in blood ketone or glucose levels, however, had a significantly lower hepatic δ13 C-PAM value than WD fed rats; suggestive of lower DNL. In summary, we show that triacetin has the potential to blunt weight gain and adipose tissue accumulation in a rodent model of obesity, possibly due to a decrease in DNL.

Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice.

A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4-6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.

Effects on Fetal Metabolic Programming and Endocannabinoid System of a Normocaloric Diet during Pregnancy and Lactation of Female Mice with Pregestational Obesity.

Fetal programming provides explanatory mechanisms for the currently high prevalence of gestational obesity. The endocannabinoid system (ECS) participates in the regulation of energy balance, and with a high-fat diet (HFD), it is overactivated. The aim of this study was to determine the effects of a nutritional intervention during pregnancy and lactation on obese female progenitors, on metabolic alterations of the offspring and on the involvement of ECS. Female mice (C57/BL/6-F0), 45 days old, and their offspring (males) were separated according to type of diet before and during gestation and lactation: CON-F1: control diet; HFD-F1 group: HFD (fat: 60% Kcal); INT-F1 group: HFD until mating and control diet (fat: 10% Kcal) afterward. Glucose tolerance and insulin sensitivity (IS) were tested at 2 and 4 months. At 120 days, mice were sacrificed, plasma was extracted for the determination of hormones, and livers for gene expression and the protein level determination of ECS components. INT-F1 group presented a lower IS compared to CON-F1, and normal levels of adiponectin and corticosterone in relation to the HFD-F1 group. The intervention increased hepatic gene expression for fatty-acid amide hydrolase and monoacylglycerol lipase enzymes; however, these differences were not observed at the protein expression level. Our results suggest that this intervention model normalized some hormonal parameters and hepatic mRNA levels of ECS components that were altered in the offspring of progenitors with pre-pregnancy obesity.

Potential Clinical Applications of Pro-Resolving Lipids Mediators from Docosahexaenoic Acid.

Docosahexaenoic acid (C22:6n-3, DHA) is the precursor of specialized pro-resolving lipid mediators (SPMs), such as resolvin, protectin, and maresin families which have been considered therapeutic bioactive compounds for human health. Growing evidence indicates that DHA and SPMs are beneficial strategies in the amelioration, regulation, and duration of inflammatory processes through different biological actions. The present review discusses the reported therapeutic benefits of SPMs on various diseases and their potential clinical applications.

Effect of a pescetarian and vegan diet on fatty acid composition in blood and spermatozoa in young healthy men.

INTRODUCTION: There is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men. METHODS: Four groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content. RESULTS: Main findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group. CONCLUSION: Higher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men.

Linoleic and arachidonic fatty acids and their potential relationship with inflammation, pregnancy, and fetal development.

BACKGROUND: A healthy maternal diet must consider an appropriate supply of long-chain polyunsaturated fatty acids (LCPUFAs) precursors to ensure adequate growth and development of the fetus. In this regard, n-6 PUFAs, predominantly linoleic (C18:2 n-6, LA) and arachidonic acid (C20:4 n-6), have a central role in the development of the central nervous system because they are part of the membrane structure and participate in the metabolism and signal transduction of cells. Nevertheless, they can also be transformed into inflammatory metabolites promoting the pathogenesis of cardiovascular diseases, cancer, and autoimmune or inflammatory conditions. In modern westernized societies, there is a high dietary consumption of foods rich in n-6 PUFAs which could have detrimental consequences for the fetus and neonate due to excessive exposure to these fatty acids (FAs). OBJECTIVE: To summarize the evidence of maternal, placental, and fetal alterations that an excessive intake of n-6 polyunsaturated FAs (PUFAs), LA, and AA), could produce during pregnancy. METHODS: A thorough review of the literature regarding the effects of n-6 PUFAs during pregnancy and lactation including in vivo and in vitro models, was carried out using the PubMed database from the National Library of Medicine-National Institutes of Health. RESULTS: An elevated intake of n-6 PUFA, specifically LA, during pregnancy influences children's motor, cognitive, and verbal development during infancy and early childhood. Similarly, they could harm the placenta and the development of other fetal organs such as the fat tissue, liver, and cardiovascular system. CONCLUSION: Maternal diet, specifically LA intake, could have significant repercussions on fetal development and long-term consequences in the offspring, including the possibility of future metabolic and mental diseases. It would be necessary to focus on the prevention of these alterations through timely dietary interventions in the target population.

Novel 13C enrichment technique reveals early turnover of DHA in peripheral tissues.

The brain is rich in DHA, which plays important roles in regulating neuronal function. Recently, using compound-specific isotope analysis that takes advantage of natural differences in carbon-13 content (13C/12C ratio or δ13C) of the food supply, we determined the brain DHA half-life. However, because of methodological limitations, we were unable to capture DHA turnover rates in peripheral tissues. In the current study, we applied compound-specific isotope analysis via high-precision GC combustion isotope ratio mass spectrometry to determine half-lives of brain, liver, and plasma DHA in mice following a dietary switch experiment. To model DHA tissue turnover rates in peripheral tissues, we added earlier time points within the diet switch study and took advantage of natural variations in the δ13C-DHA of algal and fish DHA sources to maintain DHA pool sizes and used an enriched (uniformly labeled 13C) DHA treatment. Mice were fed a fish-DHA diet (control) for 3 months, then switched to an algal-DHA treatment diet, the 13C enriched-DHA treatment diet, or they stayed on the control diet for the remainder of the study time course. In mice fed the algal and 13C enriched-DHA diets, the brain DHA half-life was 47 and 46 days, the liver half-life was 5.6 and 7.2 days, and the plasma half-life was 4.7 and 6.4 days, respectively. By using improved methodologies, we calculated DHA turnover rates in the liver and plasma, and our study for the first time, by using an enriched DHA source (very high δ13C), validated its utility in diet switch studies.

The Role of Omega-3 Polyunsaturated Fatty Acids and Their Lipid Mediators on Skeletal Muscle Regeneration: A Narrative Review.

Skeletal muscle is the largest tissue in the human body, comprising approximately 40% of body mass. After damage or injury, a healthy skeletal muscle is often fully regenerated; however, with aging and chronic diseases, the regeneration process is usually incomplete, resulting in the formation of fibrotic tissue, infiltration of intermuscular adipose tissue, and loss of muscle mass and strength, leading to a reduction in functional performance and quality of life. Accumulating evidence has shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their lipid mediators (i.e., oxylipins and endocannabinoids) have the potential to enhance muscle regeneration by positively modulating the local and systemic inflammatory response to muscle injury. This review explores the process of muscle regeneration and how it is affected by acute and chronic inflammatory conditions, focusing on the potential role of n-3 PUFAs and their derivatives as positive modulators of skeletal muscle healing and regeneration.

Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function.

Maternal obesity and the imbalance in linoleic acid (C18:2 n-6, LA) and alpha-linolenic acid (C18:3 n-3, ALA) levels are related with hepatic disturbances in the offspring. However, whether these alterations are present during fetal life is not well understood. Obese and normal weight pregnant women were recruited to determine fatty acids (FAs) consumption, FAs profile (in maternal erythrocytes, placenta and neonatal very low-density lipoproteins VLDL) and biomarkers of fetal liver function, such as gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and albumin, in umbilical cord blood. Stearic acid (C18:0, ST) was lower, and total n-3 FAs tended to be lower in umbilical cord VLDLs of obese women compared to controls. Independently of maternal obesity, GGT levels in umbilical cord blood was positively correlated with the LA content and negatively correlated with the ALA content in maternal erythrocytes. We conclude that maternal obesity and its imbalance of LA and ALA are associated with changes in biomarkers of fetal liver function.

Efficacy of Submicron Dispersible Free Phytosterols on Non-Alcoholic Fatty Liver Disease: A Pilot Study.

BACKGROUND: No pharmacological treatment is yet approved for non-alcoholic fatty liver disease (NAFLD). Plant sterols have shown healthy properties beyond lowering LDL-cholesterol, including lowering triglycerides and lipoprotein plasma levels. Despite pre-clinical data suggesting their involvement in liver fat control, no clinical study has yet been successful. AIMS: Testing a sub-micron, free, phytosterol dispersion efficacy on NAFLD. METHODS: A prospective, uncontrolled pilot study was carried out on 26 patients with ≥17.4% liver steatosis quantified by magnetic resonance imaging. Subjects consumed daily a sub-micron dispersion providing 2 g of phytosterols. Liver fat, plasma lipids, lipoproteins, liver enzymes, glycemia, insulinemia, phytosterols, liposoluble vitamins and C-reactive protein were assessed at baseline and after one year of treatment. RESULTS: Liver steatosis relative change was -19%, and 27% of patients reduced liver fat by more than 30%. Statistically and clinically significant improvements in plasma triglycerides, HDL-C, VLDL and HDL particle number and C-reactive protein were obtained, despite the rise of aspartate aminotransferase, glycemia and insulinemia. Though phytosterol plasma levels were raised by >30%, no adverse effects were presented, and even vitamin D increased by 23%. CONCLUSIONS: Our results are the first evidence in humans of the efficacy of submicron dispersible phytosterols for the treatment of liver steatosis, dyslipidemia and inflammatory status in NAFLD.

Cellular Functional, Protective or Damaging Responses Associated with Different Redox Imbalance Intensities: A Comprehensive Review.

Reactive species (RS) are produced in aerobic and anaerobic cells at different concentrations and exposure times, which may trigger diverse responses depending on the cellular antioxidant potential and defensive devices. Study searches were carried out using the PubMed database of the National Library of Medicine-National Institutes of Health. Cellular RS include reactive oxygen (ROS), nitrogen (RNS), lipid (RLS) and electrophilic species that determine either cell homeostasis or dysfunctional biomolecules. The complexity of redox signalling is associated with the variety of RS produced, the reactivity of the target biomolecules with RS, the multiplicity of the counteracting processes available, and the exposure time. The continuous distortion in the prooxidant/ antioxidant balance favoring the former is defined as oxidative stress, whose intensity determines (i) the basal not harmful unbalance (oxidative eustress) at RS levels in the pM to nM range that supports physiological processes (e.g., immune function, thyroid function, insulin action) and beneficial responses to external interventions via redox signalling; or (ii) the excessive, toxic distortion (oxidative distress) at RS levels exceeding those in the oxidative eustress zone, leading to the unspecific oxidation of biomolecules and loss of their functions causing cell death with associated pathological states. The cellular redox imbalance is a complex phenomenon whose underlying mechanisms are beginning to be understood, although how RS initiates cell signalling is a matter of debate. Knowledge of this aspect will provide a better understanding of how RS triggers the pathogenesis and progression of the disease and uncover future therapeutic measures.