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.

Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.

BACKGROUND: Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. METHODS: Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). RESULTS: HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities, oxidative stress-related parameters, and tissue n-3 LCPUFA content was observed in HT-treated rats over control animals. CONCLUSIONS: HT supplementation prevents metabolic alterations in desaturase activities, oxidative stress status, and n-3 LCPUFA content in the liver and extrahepatic tissues of mice fed HFD.

Salvia hispanica L. (chia) seed improves redox state and reverts extracellular matrix collagen deposition in skeletal muscle of sucrose-rich diet-fed rats.

Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle.

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.

Suppression of high-fat diet-induced obesity-associated liver mitochondrial dysfunction by docosahexaenoic acid and hydroxytyrosol co-administration.

OBJECTIVE: Obesity-induced by high-fat diet (HFD) is associated with liver steatosis, oxidative stress and mitochondrial dysfunction, which can be eluded by the co-administration of the lipid metabolism modulator docosahexaenoic acid (DHA) and the antioxidant hydroxytyrosol (HT). METHODS: C57BL/6J mice fed a HFD were orally administered either with vehicle, DHA, HT or DHA+HT for 12 weeks. We measured parameters related to insulin resistance, serum lipid levels, liver fatty acid (FA) content and steatosis score, concomitantly with those associated with mitochondrial energy functions modulated by the transcriptional coactivator PGC-1a. RESULTS: HFD induced insulin resistance, liver steatosis with n-3 FA depletion, and loss of mitochondrial respiratory functions with diminished NAD+/NADH ratio and ATP levels compared with CD, with the parallel decrease in the expression of the components of the PGC-1α cascade, namely, PPAR-α, FGF21 and AMPK, effects that were not observed in mice subjected to DHA and HT co-administration. CONCLUSIONS: Data presented indicate that the combination of DHA and HT prevents the development of liver steatosis and the associated mitochondrial dysfunction induced by HFD, thus strengthening the significance of this protocol as a therapeutic strategy avoiding disease evolution into more irreversible forms characterised by the absence of adequate pharmacological therapy in human obesity.

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.

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.

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.

Riesgo cardiovascular y estilo de vida en pacientes adultos de un sanatorio privado de la ciudad de Santa Fe / Cardiovascular risk and lifestyle in adult patients of a private sanatorium in the city of Santa Fe

Resumen Introducción: un estilo de vida saludable evitará la aparición de factores de riesgo de enfermedad cardiovascular (ECV), permitiendo mayor longevidad y calidad de vida. Objetivo: determinar el riesgo cardiovascular (RCV) y los componentes de salud cardiovascular en pacientes adultos que concurren a un sanatorio privado de la ciudad de Santa Fe. Materiales y método: estudio descriptivo de corte transversal. Se incluyeron pacientes (40-75 años, ambos sexos) que concurrieron espontáneamente a un sanatorio privado de la ciudad de Santa Fe entre agosto 2021-julio 2022. Se excluyeron pacientes con ECV. Mediante entrevista personal, telefónica y datos de la historia clínica, se calculó el RCV (calculadora OPS/OMS) y se evaluaron componentes de salud cardiovascular según la American Heart Association (AHA): presión arterial (PA) sistólica <130 mmHg y/o diastólica <85 mmHg), colesterol (<200 mg/dL), glucemia (<100 mg/dL), índice de masa corporal (IMC) (<65 años: 18,5-25 kg/m2; >65 años: 22-27 kg/m2), consumo frutas y verduras (≥5 porciones/día), actividad física (nivel moderado/alto), tabaquismo (no fumar/no ex fumador) y sueño, dormir 6-8hs nocturnas. Se evaluó estrés, ansiedad y depresión. Resultados expresados en frecuencias (IC 95%). Se utilizó el programa InfoStat. Resultados: participaron 94 pacientes, 44% sexo femenino (53,4±8,2 años). El 21,3% de los pacientes presentó RCV alto y 5,5% muy alto. Solo 18,9% presentó PA adecuada y 21,4% se clasificó en la categoría normopeso. El 53,6% presentó colesterol deseable y 54,4% glucemia deseable. Entre las conductas de estilo de vida: 84,2% no era fumador. Del total que respondieron las encuestas telefónicas, 13,3% consume ≥5 porciones/día de frutas y verduras, 59,6% presentó nivel moderado/alto de actividad física, 52% durmió las horas recomendadas. El 52,9% presentó bajo nivel de estrés y 53,3% no manifestó síntomas de ansiedad. Conclusión: la mayor parte de los pacientes se clasificaron en las categorías de bajo a moderado RCV con elevada frecuencia de factores de riesgo (PA elevada, exceso de peso, glucemia y colesterol elevados). Es necesario modificar conductas para mejorar el estilo de vida (consumo de frutas y verduras, nivel de actividad física, duración del sueño y los síntomas de estrés y ansiedad) para reducir el RCV.

Abstract Introduction: a healthy lifestyle will prevent the appearance of risk factors for cardiovascular disease (CVD), allowing greater longevity and quality of life. Objective: the aim of this study was to determine cardiovascular risk (CVR) and components of cardiovascular health in adult patients attending a private sanatorium in the city of Santa Fe. Materials and method: analytical, cross-sectional study. Patients (40-75 years old, both sexes) who spontaneously attended a private sanatorium in the city of Santa Fe between August 2021 and July 2022 were included. Patients with CVD were excluded. Through personal interviews, telephone interviews and medical records, CVR was calculated (PAHO/WHO calculator) and cardiovascular health components were evaluated according to the American Heart Association (AHA): systolic blood pressure (BP) <130 mmHg and/or diastolic <85 mmHg), cholesterol (<200 mg/dL), blood glucose (<100 mg/dL), body mass index (BMI) ( <65 years: 18.5-25 kg/m2; >65 years: 22-27 kg/m2), consumption of fruits and vegetables (≥5 servings/day), physical activity (moderate/high level), smoking (non-smoking/non-ex-smoker) and sleep, sleeping 6-8 hours at night. Stress, anxiety, and depression were assessed. Results expressed in frequencies (95% CI). The InfoStat program was used. Results: 94 patients participated, 44% female (53.4±8.2 years). 21.3% of patients had high CVR and 5.5% had very high CVR. Only 18.9% had adequate BP and 21.4% were classified in the normal weight category. A total of 53.6% had desirable cholesterol and 54.4% had desirable blood glucose. Among lifestyle behaviors: 84.2% were non-smokers. Of the total who answered the telephone surveys, 13.3% consumed ≥5 servings/day of fruits and vegetables, 59.6% had a moderate/high level of physical activity, and 52% slept the recommended hours. 52.9% had a low level of stress and 53.3% did not show symptoms of anxiety. Conclusion: most of the patients were classified into the categories of low to moderate CVR with a high frequency of risk factors (high BP, excess weight, high blood glucose and high cholesterol). Lifestyle modifications (fruit and vegetable intake, level of physical activity, sleep duration, and symptoms of stress and anxiety) are needed to reduce CVR

Molecular adaptations underlying the beneficial effects of hydroxytyrosol in the pathogenic alterations induced by a high-fat diet in mouse liver: PPAR-α and Nrf2 activation, and NF-κB down-regulation.

SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by an increment in the liver fat content, with a concomitant reduction in the content of n-3-long chain polyunsaturated fatty acids (n-3 LCPUFAs), downregulation of PPAR-α activity, and upregulation of NF-κB activity, effects that induce pro-lipogenic and pro-inflammatory responses. Hydroxytyrosol (HT), a polyphenol with cytoprotective effects present in extra virgin olive oil, improves the cellular antioxidant capacity for activation of transcription factor Nrf2. The objective of this work is to evaluate the molecular adaptations involved in the anti-lipogenic, anti-inflammatory, and anti-oxidant effects of HT supplementation in high-fat diet (HFD)-fed mice. METHODS AND RESULTS: Male C57BL/6J mice received (i) control diet (10% fat); (ii) control diet + HT (daily doses of 5 mg per kg body weight), (iii) HFD (60% fat); or (iv) HFD + HT for 12 weeks. HFD-fed mice exhibited (i) liver steatosis; (ii) inflammation; (iii) oxidative stress; and (iv) depletion of n-3 LCPUFAs, together with down-regulation of PPAR-α and Nrf2, and up-regulation of NF-κB. HT supplementation attenuated the metabolic alterations produced by HFD, normalizing the activity of Nrf2, reducing the drop in activity of PPAR-α, and attenuating increment of NF-κB activation. CONCLUSION: Supplementation with HT activating transcription factors PPAR-α and Nrf2, along with the deactivation of NF-κB, may reduce the liver alterations induced in HFD-fed mice.

Dietary soy protein improves adipose tissue dysfunction by modulating parameters related with oxidative stress in dyslipidemic insulin-resistant rats.

The present study investigates the benefits of the dietary intake of soy protein on adipose tissue dysfunction in a rat model that mimics several aspects of the human metabolic syndrome. Wistar rats were fed a sucrose-rich diet (SRD) for 4 months. After that, half of the animals continued with SRD until month 8 while in the other half, casein protein was replaced by isolated soy protein for 4 months (SRD-S). A reference group consumed a control diet all the time. In adipose tissue we determined: i) the activities of antioxidant enzymes, gene expression of Mn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glutathione redox state ii) the activity of xanthine oxidase (XO), ROS levels and the gene expression of NAD(P)H oxidase iii) the expression of the nuclear factor erythroid-2 related factor-2 (Nrf2). Besides, adiposity visceral index, insulin sensitivity, and tumor necrosis factor-α (TNF-α) in plasma were determined. Compared with the SRD-fed rats, the animals fed a SRD-S showed: activity normalization of SOD and glutathione reductase, improvement of mRNA SOD and normalization of mRNA GPx without changes in the expression of the Nrf2, and improvement of glutathione redox state. These results were accompanied by a normalization of XO activity and improvement of both the ROS production as well as TNF-α levels in plasma. Besides, adipocyte size distribution, adiposity visceral index and insulin sensitivity improved. The results suggest that soy protein can be a complementary nutrient for treating some signs of the metabolic syndrome.

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.

Effects of post-suckling n-3 polyunsaturated fatty acids: prevention of dyslipidemia and liver steatosis induced in rats by a sucrose-rich diet during pre- and post-natal life.

The interaction between fetal programming and the post-natal environment suggests that the post-natal diet could amplify or attenuate programmed outcomes. We investigated whether dietary n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) at weaning resulted in an amelioration of dyslipidemia, adiposity and liver steatosis that was induced by a sucrose-rich diet (SRD; where the fat source is corn oil) from the onset of pregnancy up to adulthood. During pregnancy and lactation, dams were fed an SRD or the standard powdered rodent commercial diet (RD). At weaning and until 150 days of life, male offspring from SRD-dams were divided into two groups and fed an SRD or SRD-with-fish oil [where 6% of the corn oil was partially replaced by fish oil (FO) 5% and corn oil (CO) 1%], forming SRD-SRD or SRD-FO groups. Male offspring from RD-dams continued with RD up to the end of the experimental period, forming an RD-RD group. The presence of FO in the weaning diet showed the following: prevention of hypertriglyceridemia and liver steatosis, together with increased lipogenic enzyme activity caused by a maternal SRD; the complete normalization of CPT I activity and PPARα protein mass levels; a slight but not statistically significant accretion of visceral adiposity; and limited body fat content and reduced plasma free fatty acid levels. All of these results were observed even in the presence of a high-sucrose diet challenge after weaning. SRD-dams' breast milk showed a more saturated fatty acid composition. These results suggest the capacity of n-3 PUFAs to overcome some adverse outcomes induced by a maternal and post-weaning sucrose-rich diet.

TRANS FATTY ACIDS MODIFY NUTRITIONAL PARAMETERS AND TRIACYLGLYCEROL METABOLISM IN RATS: DIFFERENTIAL EFFECTS AT RECOMMENDED AND HIGH-FAT LEVELS.

INTRODUCTION: there is still little evidence on the metabolic trans fatty acids (TFA) effects at recommended fat levels. OBJECTIVE: to investigate the differential TFA effects on some nutritional parameters, TFA retention, and triacylglycerol (TAG) regulation in rats fed recommended and high-fat diets. METHODS: male Wistar rats were fed (30 days) diets containing recommended (7%,w/w) or high-fat (20%,w/w) levels, supplemented or not with TFA (C7, C20, TFA7 and TFA20). RESULTS: TFA7 (vs.C7) rats showed an increased body weight associated with higher fat pads and liver and serum TAG. The hypertriacylglyceridaemia was related to a decreased muscle LPL activity, while the higher hepatic TAG content was associated with both an increased SREBP-1c gene expression and ACC activity, and a reduced CPT-Ia gene expression. The TFA20 diet did not potentiate the higher body weight, fat pads and TAG levels induced by the C20 diet. Although the hepatic TAG-secretion rate (TAG-SR) increased by TFA20 vs. C20, the same triacylglyceridaemia was associated with a compensatory increase of the adipose tissue LPL activity. The attenuated hepatic TAG accretion in TFA20 was related to an increase of TAG-SR and to a lower increase of SREBP-1c and SCD1 mRNA expressions, paralleled to a relative decrease of SCD1 index and ACC activity. DISCUSSION AND CONCLUSION: TFA alters nutritional parameters and lipid metabolism in rats. However, different responses to the TFA on TAG levels and their regulation were observed between rats fed recommended and high-fat diets. These divergences might be related to different tissue TFA retentions and rumenic acid bioconversion.

Introducción: existen escasas evidencias sobre los efectos metabólicos de los AGT a niveles recomendados de grasa. Objetivo: investigar los efectos diferenciales de los ácidos grasos trans (TFA) sobre parámetros nutricionales, retención de TFA y regulación de triacilglicéridos (TAG) en ratas alimentadas con niveles recomendados o elevados de grasa. Métodos: ratas macho Wistar fueron alimentadas (30 días) con dietas que contenían un 7% o 20% de grasas suplementadas o no con TFA (C7-C20-TFA7-TFA20). Resultados: TFA7 (vs. C7) incrementó el peso corporal asociado a mayores panículos adiposos y TAG. La hipertriacilgliceridemia fue relacionada con una menor actividad LPL muscular, y el incrementado TAG hepático con una elevada expresión génica de SREBP-1c y actividad ACC, y reducida expresión génica de CPT-Ia. Los TFA no potenciaron los elevados pesos corporales, los panículos adiposos y los TAG inducidos por C20. Aunque la secreción hepática de TAG (TAG-SR) incrementó en TFA20 vs. C20, la similar triacilgliceridemia fue asociada a un compensatorio incremento de la actividad LPL en tejido adiposo. La atenuada acumulación hepática de TAG en TFA20 estuvo relacionada con una incrementada TAG-SR y un menor incremento de la expresión génica de SREBP-1c y SCD1, paralela a un relativo descenso del índice SCD1 y de la actividad ACC. Discusión y conclusión: los TFA alteran los parámetros nutricionales y lipídicos en ratas. Sin embargo, diferentes respuestas sobre los niveles y regulación de los TAG por los TFA fueron observadas entre ratas alimentadas con niveles recomendados y elevados de grasa dietaria. Estas divergencias pueden estar relacionadas con diferentes retenciones de TFA y su bioconversión a ácido ruménico.

Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats.

The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the time course of the development of oxidative stress, changes in proinflammatory cytokines and adiponectin levels, and their relationship with insulin resistance. We analyzed the morphometric characteristics of epididymal adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant defense, inflammatory mediators, adiponectin levels and insulin resistance in rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a control diet. The results showed a depletion of antioxidant enzyme activities in the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet. Superoxide dismutase activity and the redox state of glutathione showed a significant decrease at weeks 15 and 30. This was accompanied by visceral adiposity and enhanced lipogenic enzyme activities. An increase in the plasma levels of proinflammatory markers (TNF-α and IL-6) was recorded only after 30 weeks on the diet. A reduction in plasma adiponectin levels accompanied the time course of deterioration of whole-body insulin sensitivity. The results suggest that lipid peroxidation, depletion of antioxidant defenses and changes in inflammatory cytokines induced by a sucrose-rich diet contribute to the dysregulation of adipose tissue and insulin resistance. Finally, these results show that the progressive deterioration of adipose tissue function, which begins in the absence of both visceral adiposity and overweight, is highly dependent on the length of time on the diet.

Refeeding with conjugated linoleic acid increases serum cholesterol and modifies the fatty acid profile after 48 hours of fasting in rats.

There is no consensus about the effects of conjugated linoleic acid (CLA) on lipid metabolism, especially in animals fed a high-fat diet. Therefore, the objective of the present study was to evaluate the incorporation of CLA isomers into serum, liver and adipose tissue, as well as the oxidative stress generated in rats refed with high-fat diets after a 48 hour fast. Rats were refed with diets containing soybean oil, rich in linoleic acid [7% (Control Group - C) or 20% (LA Group)], CLA [CLA Group - 20% CLA mixture (39.32 mole% c9,t11-CLA and 40.59 mole% t10,c12- CLA)], soybean oil + CLA (LA+CLA Group - 15.4% soybean oil and 4.6% CLA) or animal fat (AF, 20% lard). The CLA group showed lower weight gain and liver weight after refeeding, as well as increased serum cholesterol. The high dietary fat intake induced fat accumulation and an increase in -tocopherol in the liver, which were not observed in the CLA group. Circulating -tocopherol was increased in the CLA and CLA+LA groups. The high- fat diets reduced liver catalase activity. CLA isomers were incorporated into serum and tissues. In this shortterm refeeding experimental model, CLA prevented hepatic fat accumulation, although it produced an increase in serum cholesterol.

No hay consenso acerca de los efectos del ácido linoleico conjugado (CLA) sobre el metabolismo lipídico, especialmente en animales alimentados con una dieta alta en grasa. Por lo tanto, el objetivo del presente estudio fue evaluar la incorporación de isómeros de CLA en el suero, hígado y tejido adiposo, así como el estrés oxidativo generado en ratas realimentadas con dietas altas en grasa después de 48 horas de ayuno. Los animales fueron realimentados con dietas que contenían aceite de soja, rico en ácido linoleico [7% (Groupo Control - C)], o 20% (Groupo LA)], CLA [Groupo CLA - 20% de mezcla de CLA (39,32% moles del c9,t11-CLA y 40.59% moles del t10,c12-CLA)], aceite de soja + CLA (Grupo LA+- CLA - 15.4 % de aceite de soja y 4,6% de CLA) o grasa animal (Grupo AF, 20% de manteca de cerdo). El grupo CLA tuvo menor aumento de peso y menor peso hepático después de la realimentación, así como aumento del colesterol total em el suero. La dieta alta en grasa indujo la acumulación de grasa y un aumento de -tocoferol en el hígado, que no se observaron en el grupo CLA. El -tocoferol serico fue mayor en los grupos CLA y LA+CLA. Las dietas altas en grasa redujeron la actividad de la catalasa hepática. Isómeros de CLA fueron incorporados em el suero y tejidos. En este modelo de realimentación de corto prlazo, el CLA ha impedido la acumulación de grasa hepática, aunque genero un aumento del colesterol total sérico.

Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profile during protein repletion in rats.

Protein depletion is associated with hepatic steatosis and decreased circulating triacylglycerol (TAG). Since conjugated linoleic acid (CLA) increases lean body mass, protects against muscle catabolism, and modulates lipid metabolism, the aim of this work was to investigate the effects of CLA with two different amounts of dietary fat on the regulation of plasma and hepatic TAG concentration, and its possible connections with changes in fatty acid (FA) profile in plasma, liver and adipose tissue and hepatic oxidative status during protein repletion. Rats were fed a low protein diet (14 days) and then a protein repletion diet (30 days), supplemented or not with CLA, containing 7% (w/w) or 20% (w/w) of fat. Hepatic TAG secretion and removal by muscle and adipose tissue lipoprotein lipase, FA profile and liver oxidative status were evaluated. Protein depletion affected hepatic TAG secretion and peripheral removal, decreasing plasma and increasing liver TAG concentration, whereas protein repletion with CLA improved these abnormalities independently of the amount of dietary fat by increasing hepatic TAG secretion. This prevention in the absence of CLA was not observed. CLA was incorporated in plasma and tissues (adipose > liver > plasma, and c9,t11-CLA > t10,c12-CLA), accompanied by alterations in FA composition, mainly in adipose tissue. The hepatic oxidative stress was overcome by protein repletion. CLA had a beneficial impact on TAG metabolism in protein repleted animals, preventing hepatic steatosis through higher hepatic TAG secretion.