Fossil Collection at the Zoology Museum of the University of Concepción: enhancing understanding of Chile's past biodiversity.

Background: The digital inventory of paleontological material stored in Chilean museums is highly relevant as it increases accessibility to information, both locally and over long distances, while reducing wear and tear on specimens caused by physical manipulation. The Fossil Collection database of the Museum of Zoology of the University of Concepción (UCC_MZUC_FOS) includes 144 records, with the main representatives being marine invertebrates of the Bivalvia, Echinoidea and Gastropoda classes. Notable species include Encopecalderensis, Hemiasterwayensis, Zygochlamyspatagonica and Retrotapesexalbidus, most of which come from important Chilean fossil sites. Material was collected between 1970 and 2017, with a large portion of it being donated and identified by Professor Emeritus Hugo I. Moyano and Dr. Alberto Larraín. Although the specimens contained in the resource offer basic collecting information, they substantially contribute to sharing knowledge on the fossils kept in the museums throughout the country, while providing data on their distribution. New information: This resource corresponds to the first publication of data on faunal fossils from a museum collection in Chile on the Global Biodiversity Information Facility (GBIF) platform, thereby enhancing the understanding and documentation of Chile's paleontological heritage and its national biodiversity.

Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

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.

A Feasible Approach to Developing Fiber-Enriched Bread Using Pomegranate Peel Powder: Assessing Its Nutritional Composition and Glycemic Index.

The consumption of dietary fiber (DF) has been associated with a reduced incidence of non-communicable diseases. Despite various strategies implemented worldwide to increase DF intake, it remains low. Therefore, the development of new fiber-rich food products that are widely consumed could be a strategy to improve DF intake. In this study, an agro-industrial by-product, pomegranate peel powder (PPP), was used as an innovative source of DF and antioxidant. The objective was to develop a bread enriched with DF, antioxidants, and sensory characteristics by partially replacing wheat flour (WF) with PPP at levels of 0%, 2.5%, 5%, 7.5%, and 10%. Bread with 2.5% and 5% PPP was chosen for a clinical trial to evaluate glycemic response (GR) in healthy subjects and determine the bread's glycemic index (GI). As the percentage of PPP increased, both the DF and total polyphenol content increased significantly. The highest overall acceptability was achieved with bread containing up to 5% PPP. Consumption of bread with 2.5% and 5.0% PPP significantly reduced the GI compared to the control bread, while the decrease in GR was not significant. PPP could be a potential food and low-cost ingredient to improve the bread's nutritional quality through its contribution to DF and antioxidants.

Targeting Mitochondria for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: Polyphenols as a Non-pharmacological Approach.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) has a high and growing prevalence globally. Mitochondria are fundamental in regulating cell energy homeostasis. Nevertheless, mitochondria control mechanisms can be exceeded in this context of energy overload. Damaged mitochondria worsen NAFLD progression. Diet and lifestyle changes are the main recommendations for NAFLD prevention and treatment. Some polyphenols have improved mitochondrial function in different NAFLD and obesity models. OBJECTIVE: The study aims to discuss the potential role of polyphenols as a nonpharmacological approach targeting mitochondria to prevent and treat NAFLD, analyzing the influence of polyphenols' chemical structure, limitations and clinical projections. METHODS: In vivo and in vitro NAFLD models were considered. Study searches were performed using the following keywords: nonalcoholic fatty liver disease, liver steatosis, mitochondria, mitochondrial activity, mitochondrial dynamics, mitochondrial dysfunction, mitochondrial morphology, mitochondrial cristae, fusion, fission, polyphenols, flavonoids, anthocyanins, AND/OR bioactive compounds. CONCLUSION: Polyphenols are a group of diverse bioactive molecules whose bioactive effects are highly determined by their chemical structure. These bioactive compounds could offer an interesting non-pharmacological approach to preventing and treating NAFLD, regulating mitochondrial dynamics and function. Nevertheless, the mitochondria' role in subjects with NAFLD treatment is not fully elucidated. The dosage and bioavailability of these compounds should be addressed when studied.

N-3 PUFAs and their specialized pro-resolving lipid mediators on airway inflammatory response: beneficial effects in the prevention and treatment of respiratory diseases.

Respiratory diseases include a wide range of pathologies with different clinical manifestations, affecting the normal airways and lung function. An increase in the inflammatory response is considered a characteristic hallmark of these diseases, being also a critical factor for their progression. The n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (C20:4n-3, EPA), docosahexaenoic acid (C22:6n-3, DHA) and their lipid mediators are known to have an inflammation pro-resolution effect. The effects of these n-3 PUFAs in the prevention and treatment of respiratory diseases are beginning to be understood. Consequently, this article aims to analyze the influence of n-3 PUFAs and their lipid mediators on the inflammatory response in respiratory health, emphasizing recent data concerning their beneficial effects in the prevention and possible treatment of different respiratory diseases, particularly asthma, airway allergic syndromes and chronic obstructive pulmonary disease. The review includes studies regarding the effects of EPA, DHA, and their specialized pro-resolving lipid mediators (SPMs) on in vivo and in vitro models of respiratory disease, concluding that EPA and DHA have a positive impact in attenuating the pro-inflammatory response in respiratory diseases, reducing symptoms like nasal congestion, fever and difficulty in breathing. Controversial data reported are probably due to differences in several factors, including the dosages, administration vehicles, and the supplementation times employed, which are aspects that remain to be addressed in future studies.

Potencial efecto terapéutico de los polifenoles obtenidos de la cáscara de granada en la esteatosis hepática

RESUMEN Antecedentes: La enfermedad por hígado graso no alcohólico (EHGNA) tiene una elevada prevalencia a nivel mundial, y puede ir desde la esteatosis simple hasta hepatocarcinoma. Su origen es multifactorial, siendo la dieta poco saludable un factor clave en su patogenia y progresión. Los polifenoles son antioxidantes que han mostrado beneficios en el tratamiento de la EHGNA. Una fuente emergente de estos compuestos son los residuos agroindustriales, entre ellos, la cáscara de granada. La cáscara de granada tiene un alto contenido de polifenoles, específicamente de elagitaninos. Su extracto fenólico (extracto de cáscara de granada; ECG) ha mostrado efectos promisorios a nivel metabólico. Sin embargo, su uso presenta algunas limitantes que deben ser consideradas antes de recomendar su ingesta mediante alimentos funcionales o nutracéuticos para prevención o tratamiento de EHGNA. Objetivo: Discutir a partir de datos obtenidos en estudios in vitro y modelos animales, el potencial terapéutico de los polifenoles obtenidos de la cáscara de granada para prevención y tratamiento de la EHGNA. Metodología: Se realizó una búsqueda bibliográfica en bases de datos PubMed y Web of Science (2015 a la fecha) de estudios en modelos de esteatosis hepática in vitro y en animales, además de ensayos clínicos relacionados. Conclusión: Existen datos promisorios sobre el uso del ECG en alteraciones metabólicas propias de la EHGNA y esteatosis hepática, principalmente a nivel de perfil lipídico. Se deben discutir las dosis y formas de administración, con el fin de mejorar su estabilidad y biodisponibilidad. Se requieren ensayos clínicos controlados que confirmen los efectos en humanos.

ABSTRACT Background: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and can range from simple steatosis to hepatocarcinoma. Its causes are multifactorial, with an unhealthy diet being a key factor in its pathogenesis and progression. Polyphenols are antioxidants that have shown benefits in treating NAFLD. An emerging source of these compounds is agro-industrial by-products, including pomegranate peels. Pomegranate peels are high in polyphenols, specifically ellagitannins. Its polyphenolic extract (PPE) has shown promising metabolic benefits. However, its use has some limitations that must be considered before recommending its intake through functional foods or nutraceuticals to prevent or treat NAFLD. Objective: This article aims to discuss, using results from in vitro studies and animal models, the therapeutic potential of polyphenols obtained from pomegranate peels to prevent and treat NAFLD. Methods: A bibliographic search was carried out in PubMed and Web of Science databases (2015 to date) of in vitro and animal model studies of hepatic steatosis, in addition to related clinical trials. Conclusion: There are promising data on the use of PPE in metabolic disorders typical of NAFLD and hepatic steatosis, mainly improving lipid profile. Doses and vehicles of administration should be discussed to improve stability and bioavailability. Controlled clinical trials are required to confirm the effects in humans.

Bioaccessibility of Anthocyanins on in vitro Digestion Models: Factors Implicated and Role in Functional Foods Development.

BACKGROUND: Worldwide, the prevalence of obesity and related non-communicable chronic diseases is high and continues to grow. In that sense, anthocyanins (ANC) have shown beneficial health effects in preventing obesity and metabolic risk factors. Moreover, the demand for functional foods incorporating these compounds has risen significantly in the past years. Thus, there is a need for validations of the functional properties of these formulations; nevertheless, in vivo assays are complex and require a lot of resources. One approach for estimating bioactive compounds' functionality and health benefits is to evaluate their bioaccessibility on a specific food matrix, determined by various factors. This article aims to review different factors influencing the bioaccessibility of ANC evaluated on in vitro digestion models as a functionality parameter, elucidating the effect of chemical composition, raw materials, food matrices, and vehicles for the delivery of ANC. METHODS: Study searches were performed using PubMed, Web of Science, Scopus, and Science Direct databases. RESULTS: Different factors influenced bioaccessibility and stability of ANC studied by in vitro digestion: i) the raw material used for ANC obtention; ii) food processing; iii) other food components; iv) the extraction method and solvents used; v) the structure of ANC; vi) delivery system (e.g., microencapsulation); vii) pH of the medium; viii) the digestion stage. CONCLUSION: Simulated digestion systems allow to determine free or encapsulated ANC bioaccessibility in different food matrices, which offers advantages in determining the potential functionality of a food product.

Beneficial Effects of Dietary Polyphenols in the Prevention and Treatment of NAFLD: Cell-Signaling Pathways Underlying Health Effects.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accretion of triacylglycerides in the absence of alcohol intake that may progress to steatohepatitis, fibrosis and cirrhosis, becoming the main cause of chronic liver disease. This article discusses recent data concerning the use of dietary polyphenols in the prevention and treatment of NAFLD in vitro, in vivo, and in clinical trials. METHODS: Study searches were performed using the PubMed database from the National Library of Medicine-National Institutes of Health. RESULTS: Polyphenols exert beneficial effects in NAFLD, with positive outcomes being related to body weight gain, insulin resistance, liver fat accumulation, oxidative stress, proinflammatory status, mitochondrial dysfunction and ER stress. Data reported for hydroxytyrosol suggest that the activation of the hepatic PPAR-α-FGF21-AMPK-PGC-1α signaling cascade is associated with fatty acid oxidation enhancement, de novo lipogenesis diminution and recovery of mitochondrial function, a contention that is supported by the actions of several polyphenols on specific components of this signaling pathway. Besides, polyphenols downregulate NF-κB, suppressing the pro-inflammatory state developed in NAFLD and upregulate liver Nrf2, increasing the cellular antioxidant potential. The latter feature of polyphenols is contributed by chelation of pro-oxidant trace elements, reduction of free radicals to stable forms and inhibition of free radical generating systems. CONCLUSION: Polyphenols are relevant bioactive compounds in terms of prevention and treatment of NAFLD, which exhibit low bioavailability and instability in biological systems that could limit their health effects. These drawbacks reinforce the necessity of further studies to improve the efficacy of polyphenol formulations for human interventions.

Docosahexaenoic and Arachidonic Acids as Neuroprotective Nutrients throughout the Life Cycle.

The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present review analyzes the neuroprotective role of DHA and AA in the extreme stages of life, emphasizing the importance of these LCPUFA during the first year of life and in the developing/prevention of neurodegenerative diseases associated with aging.

Polyphenols and their anti-obesity role mediated by the gut microbiota: a comprehensive review.

Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation.

Microencapsulated pomegranate peel extract induces mitochondrial complex IV activity and prevents mitochondrial cristae alteration in brown adipose tissue in mice fed on a high-fat diet.

Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterised. Eight-week-old male C57BL/6J mice (n 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + IN, HFD + PPE (50 mg/kg per d TP) and HFD + MPPE (50 mg/kg per d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (P < 0·001), fasting glycaemia (P = 0·007) and total cholesterol rise (P = 0·001). MPPE resulted in higher BAT mitochondrial complex IV activity (P = 0·03) and prevented HFD-induced mitochondrial cristae alteration (P = 0·02). In conclusion, MPPE prevented HFD-induced excessive body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with a HFD.

The metabolic dysfunction of white adipose tissue induced in mice by a high-fat diet is abrogated by co-administration of docosahexaenoic acid and hydroxytyrosol.

BACKGROUND: Nutritional interventions are promising tools for the prevention of obesity. The n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) docosahexaenoic acid (DHA) modulates immune and metabolic responses while the antioxidant hydroxytyrosol (HT) prevents oxidative stress (OS) in white adipose tissue (WAT). OBJECTIVE: The DHA plus HT combined protocol prevents WAT alterations induced by a high-fat diet in mice. Main related mechanisms. METHODS: Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) or a high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1) or both. Measurements of WAT metabolism include morphological parameters, DHA content in phospholipids (gas chromatography), lipogenesis, OS and inflammation markers, mitochondrial activity and gene expression of transcription factors SREBP-1c, PPAR-γ, NF-κB (p65) and Nrf2 (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). RESULTS: The combined DHA and HT intervention attenuated obesity development, suppressing the HFD-induced inflammatory and lipogenic signals, increasing antioxidant defenses, and maintaining the phospholipid LCPUFA n-3 content and mitochondrial function in WAT. At the systemic level, the combined intervention also improved the regulation of glucose and adipokine homeostasis. CONCLUSION: The combined DHA and HT protocol appears to be an important nutritional strategy for the treatment of metabolic diseases, with abrogation of obesity-driven metabolic inflammation and recovery of a small-healthy adipocyte phenotype.

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

OBJECTIVE: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. METHODS: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). RESULTS: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. CONCLUSION: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs. METHODS: The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health. RESULT: The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator-activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action. CONCLUSION: The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.

High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration.

High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1), or EPA + HT (50 and 5 mg kg-1 day-1, respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-γ coactivator-1α (PGC-1α) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1α signaling components, nuclear respiratory factor-2 (NRF-2) and ß-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease.

Docosahexaenoic acid and hydroxytyrosol co-administration fully prevents liver steatosis and related parameters in mice subjected to high-fat diet: A molecular approach.

Attenuation of high-fat diet (HFD)-induced liver steatosis is accomplished by different nutritional interventions. Considering that the n-3 PUFA docosahexaenoic acid (DHA) modulates lipid metabolism and the antioxidant hydroxytyrosol (HT) diminishes oxidative stress underlying fatty liver, it is hypothesized that HFD-induced steatosis is suppressed by DHA and HT co-administration. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg/kg/day), HT (5 mg/kg/day) or both. The combined DHA + HT protocol fully prevented liver steatosis and the concomitant pro-inflammatory state induced by HFD, with suppression of lipogenic and oxidative stress signaling, recovery of fatty acid oxidation capacity and enhancement in resolvin availability affording higher inflammation resolution capability. Abrogation of HFD-induced hepatic steatosis by DHA and HT co-administration represents a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time.

Hydroxytyrosol supplementation ameliorates the metabolic disturbances in white adipose tissue from mice fed a high-fat diet through recovery of transcription factors Nrf2, SREBP-1c, PPAR-γ and NF-κB.

BACKGROUND: White adipose tissue (WAT) have a relevant metabolic and inflammatory function, in overweight or obesity conditions. In this regard, the WAT under over feeding nutrition present a significant increment in oxidative stress, pro-inflammatory status and depletion of n-3 long chain polyunsaturated fatty acid. Hydroxytyrosol (HT) is a polyphenol with important cytoprotective effects, and this molecule can modulate the gene expression, transcription factors and enzymatic activity. OBJECTIVE: Therefore, the purpose of this study was evaluate the anti-inflammatory, anti-oxidant and anti-lipogenic effects of HT supplementation mice and the molecular adaptations involved, on dysfunctional WAT from high-fat diet (HFD)-fed mice. METHODS AND RESULTS: Male C57BL/6 J mice received (i) control diet (10% fat); (ii) control diet + HT (daily doses of 5 mg kg body weight), (iii) HFD (60% fat); or (iv) HFD + HT for 12 weeks. HFD-fed mice exhibited: (i) WAT hypertrophy; (ii) oxidative stress and depletion of antioxidant defenses, (iii) increased lipogenesis and pro-inflammatory status, (iv) depletion of n-3 LCPUFA and (v) up-regulation of NF-κB and SREBP 1c with down-regulation Nrf2, and PPAR-γ. HT supplementation attenuated the metabolic impairment produced by HFD in WAT, attenuating increment of NF-κB and SREBP 1c, and increasing the activity of Nrf2 and PPAR-γ. CONCLUSION: Supplementation with HT improve the WAT dysfunction induced by HDF in mice through the modulation of transcription factors NF-κB, Nrf2, SREBP-1c and PPAR-γ as well as their target genes, involved in inflammation, antioxidant defenses and lipogenesis.

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.