Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.

BACKGROUND & AIMS: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS: Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Holistic Integration of Omics Tools for Precision Nutrition in Health and Disease.

The combination of multiple omics approaches has emerged as an innovative holistic scope to provide a more comprehensive view of the molecular and physiological events underlying human diseases (including obesity, dyslipidemias, fatty liver, insulin resistance, and inflammation), as well as for elucidating unique and specific metabolic phenotypes. These omics technologies include genomics (polymorphisms and other structural genetic variants), epigenomics (DNA methylation, histone modifications, long non-coding RNA, telomere length), metagenomics (gut microbiota composition, enterotypes), transcriptomics (RNA expression patterns), proteomics (protein quantities), and metabolomics (metabolite profiles), as well as interactions with dietary/nutritional factors. Although more evidence is still necessary, it is expected that the incorporation of integrative omics could be useful not only for risk prediction and early diagnosis but also for guiding tailored dietary treatments and prognosis schemes. Some challenges include ethical and regulatory issues, the lack of robust and reproducible results due to methodological aspects, the high cost of omics methodologies, and high-dimensional data analyses and interpretation. In this review, we provide examples of system biology studies using multi-omics methodologies to unravel novel insights into the mechanisms and pathways connecting the genotype to clinically relevant traits and therapy outcomes for precision nutrition applications in health and disease.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

Consumption of caffeinated beverages and kidney function decline in an elderly Mediterranean population with metabolic syndrome.

It remains unclear whether caffeinated beverages could have deleterious renal effects in elderly population with underlying comorbid conditions. We investigated the associations between coffee, tea, or caffeine intake and 1-year changes in glomerular filtration rate (eGFR) in a large Spanish cohort of overweight/obese elderly with metabolic syndrome (MetS). This prospective analysis includes 5851 overweight/obese adults (55-75 years) with MetS from the PREDIMED-Plus study. We assessed coffee, tea, and caffeine consumption from a validated food-frequency questionnaire and creatinine-based eGFR using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariate-adjusted regression models were applied to test associations between baseline coffee, tea, or caffeine intake and 1-year eGFR changes. Caffeinated coffee (> 2 cups/day) and tea (at least 1 cup/day) drinkers had 0.88 and 0.93 mL/min/1.73 m2 greater eGFR decrease respectively, compared to those with less than 1 cup/day of coffee consumption or non-tea drinkers. Furthermore, caffeinated coffee consumption of > 2 cups/day was associated with 1.19-fold increased risk of rapid eGFR decline > 3 mL/min/1.73 m2 (95% CI 1.01-1.41). Similarly, individuals in the highest (median, 51.2 mg/day) tertile of caffeine intake had a 0.87 mL/min/1.73 m2 greater eGFR decrease. Decaffeinated coffee was not associated with eGFR changes. In conclusion, higher consumption of caffeinated coffee, tea, and caffeine was associated with a greater 1-year eGFR decline in overweight/obese adults with MetS.

Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice.

Obesity and aging are associated to non-alcoholic fatty liver disease (NAFLD) development. Here, we investigate whether long-term feeding with a docosahexaenoic acid (DHA)-enriched diet and aerobic exercise, alone or in combination, are effective in ameliorating NAFLD in aged obese mice. Two-month-old female C57BL/6J mice received control or high fat diet (HFD) for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA (15% dietary lipids replaced by a DHA-rich concentrate), DIO + EX (treadmill running), and DIO + DHA + EX up to 18 months. The DHA-rich diet reduced liver steatosis in DIO mice, decreasing lipogenic genes (Dgat2, Scd1, Srebp1c), and upregulated lipid catabolism genes (Hsl/Acox) expression. A similar pattern was observed in the DIO + EX group. The combination of DHA + exercise potentiated an increase in Cpt1a and Ppara genes, and AMPK activation, key regulators of fatty acid oxidation. Exercise, alone or in combination with DHA, significantly reversed the induction of proinflammatory genes (Mcp1, Il6, Tnfα, Tlr4) in DIO mice. DHA supplementation was effective in preventing the alterations induced by the HFD in endoplasmic reticulum stress-related genes (Ern1/Xbp1) and autophagy markers (LC3II/I ratio, p62, Atg7). In summary, long-term DHA supplementation and/or exercise could be helpful to delay NAFLD progression during aging in obesity.

Differential response to a 6-month energy-restricted treatment depending on SH2B1 rs7359397 variant in NAFLD subjects: Fatty Liver in Obesity (FLiO) Study.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is worldwide recognized as the most common cause of chronic liver disease. Current NAFLD clinical management relies on lifestyle change, nevertheless, the importance of the genetic make-up on liver damage and the possible interactions with diet are still poorly understood. The aim of the study was to evaluate the influence of the SH2B1 rs7359397 genetic variant on changes in body composition, metabolic status and liver health after 6-month energy-restricted treatment in overweight/obese subjects with NAFLD. In addition, gene-treatment interactions over the course of the intervention were examined. METHODS: The SH2B1 genetic variant was genotyped in 86 overweight/obese subjects with NAFLD from the FLiO study (Fatty Liver in Obesity study). Subjects were metabolically evaluated at baseline and at 6-months. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, a lipidomic test (OWL®-test) and specific blood liver biomarkers. Additionally, body composition, general biochemical markers and dietary intake were determined. RESULTS: Both genotypes significantly improved their body composition, general metabolic status and liver health after following an energy-restricted strategy. Liver imaging techniques showed a greater decrease in liver fat content (- 44.3%, p < 0.001) and in serum ferritin levels (p < 0.001) in the carriers of the T allele after the intervention. Moreover, lipidomic analysis, revealed a higher improvement in liver status when comparing risk vs. no-risk genotype (p = 0.006 vs. p = 0.926, respectively). Gene-treatment interactions showed an increase in fiber intake and omega-3 fatty acid in risk genotype (p interaction = 0.056 and p interaction = 0.053, respectively), while a significant increase in MedDiet score was observed in both genotype groups (p = 0.020). Moreover, no-risk genotype presented a relevant decrease in hepatic iron as well as in MUFA intake (p = 0.047 and p = 0.034, respectively). CONCLUSION: Subjects carrying the T allele of the rs7359397 polymorphism may benefit more in terms of hepatic health and liver status when prescribed an energy-restricted treatment, where a Mediterranean dietary pattern rich in fiber and other components such as omega-3 fatty acids might boost the benefits. TRIAL REGISTRATION: The Fatty Liver in Obesity was approved by the Research Ethics Committee of the University of Navarra and retrospectively registered (NCT03183193; www.clinicaltrials.gov ); June 2017.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.

BACKGROUND AND AIMS: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. METHODS: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. RESULTS: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). CONCLUSIONS: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed.

Effects of a 6-month dietary-induced weight loss on erythrocyte membrane omega-3 fatty acids and hepatic status of subjects with nonalcoholic fatty liver disease: The Fatty Liver in Obesity study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested as important biomolecules in the management of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: This study aimed to evaluate the effect of 6-month weight loss diets on erythrocyte membrane omega-3 PUFA composition of NAFLD adults, and to evaluate the potential relationship between erythrocyte membrane omega-3 PUFAs and hepatic health markers. METHODS: In this secondary analysis of the Fatty Liver in Obesity study, erythrocyte membranes were analyzed by gas chromatography in 54 subjects with liver steatosis detected by ultrasonography who achieved a weight loss >5% after the follow-up. Baseline and 6-month evaluation included hepatic acoustic radiation force impulse elastography and magnetic resonance imaging, anthropometry, body composition, and biochemical determinations. RESULTS: After the follow-up, α-linolenic acid (ALA) proportion significantly increased in erythrocyte membranes, whereas eicosapentaenoic acid (EPA) showed no statistical difference and docosapentaenoic acid decreased. Both the changes in erythrocyte membrane ALA and EPA were positively associated with dietary ALA. Regression analyses evidenced that the changes in erythrocyte membrane ALA and EPA were inversely associated with the changes in liver stiffness and liver iron content, respectively. CONCLUSION: The adherence to weight loss strategies for 6 months led to changes in erythrocyte membrane omega-3 PUFA composition, which in turn were associated with changes in hepatic markers, suggesting that these fatty acids accompany the improvements in the liver during a dietary treatment. These findings show that beyond weight loss, the composition of the diet has an important role in the management of NAFLD.

A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats.

The metabolic properties of omega-6 fatty acid consumption are being increasingly accepted. We had previously observed that supplementation with a borage seed oil (BSO), as a source of linoleic (18:2n-6; LA) and gamma-linolenic (18:3n-6; GLA) acids, reduces body weight and visceral adiposity and improves insulin sensitivity in a diet-induced obesity model of Wistar rats. Here, it was investigated whether the anti-obesogenic properties of BSO could be maintained in a pre-obese model of rats, and if these effects are enhanced by a combination with low doses of quercetin, together with its potential role in the regulation of the adipocyte biology. The combination of BSO and quercetin during 8 weeks was able to ameliorate glucose intolerance and insulin resistance, and to improve liver steatosis. Although no effects were observed on body weight, animals supplemented with this combination exhibited a lower proportion of visceral adiposity. In addition, in vitro differentiation of epididymal adipose-precursor cells of the BSO-treated animals exhibited a down-regulation of Fasn, Glut4, Pparg and Srebp1 genes, in comparison with the control group. Finally, in vitro evaluation of the components of BSO demonstrated that the anti-adipogenic activity of quercetin was significantly potentiated by the combination with both LA and GLA through the down-regulation of different adipogenesis-key genes in 3T3-L1 cells. All these data suggest that omega-6 fatty acids LA and GLA, and their natural sources such as BSO, could be combined with quercetin to potentiate their effects in the prevention of the excess of adiposity and the insulin resistance.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Modeling of an integrative prototype based on genetic, phenotypic, and environmental information for personalized prescription of energy-restricted diets in overweight/obese subjects.

BACKGROUND: Interindividual variability in weight loss and metabolic responses depends upon interactions between genetic, phenotypic, and environmental factors. OBJECTIVE: We aimed to model an integrative (nutri) prototype based on genetic, phenotypic, and environmental information for the personalized prescription of energy-restricted diets with different macronutrient distribution. METHODS: A 4-mo nutritional intervention was conducted in 305 overweight/obese volunteers involving 2 energy-restricted diets (30% restriction) with different macronutrient distribution: a moderately high-protein (MHP) diet (30% proteins, 30% lipids, and 40% carbohydrates) and a low-fat (LF) diet (22% lipids, 18% proteins, and 60% carbohydrates). A total of 201 subjects with good dietary adherence were genotyped for 95 single nucleotide polymorphisms (SNPs) related to energy homeostasis. Genotyping was performed by targeted next-generation sequencing. Two weighted genetic risk scores for the MHP (wGRS1) and LF (wGRS2) diets were computed using statistically relevant SNPs. Multiple linear regression models were performed to estimate percentage BMI decrease depending on the dietary macronutrient composition. RESULTS: After energy restriction, both the MHP and LF diets induced similar significant decreases in adiposity, body composition, and blood pressure, and improved the lipid profile. Furthermore, statistically relevant differences in anthropometric and biochemical markers depending on sex and age were found. BMI decrease in the MHP diet was best predicted at ∼28% (optimism-corrected adjusted R2 = 0.279) by wGRS1 and age, whereas wGRS2 and baseline energy intake explained ∼29% (optimism-corrected adjusted R2 = 0.287) of BMI decrease variability in the LF diet. The incorporation of these predictive models into a decision algorithm allowed the personalized prescription of the MHP and LF diets. CONCLUSIONS: Different genetic, phenotypic, and exogenous factors predict BMI decreases depending on the administration of a hypocaloric MHP diet or an LF diet. This holistic approach may help to personalize dietary advice for the management of excessive body weight using precision nutrition variables.This trial was registered at clinicaltrials.gov as NCT02737267.

Precision Nutrition and Metabolic Syndrome Management.

The journal NUTRIENTS published some time ago a special issue about "Precision Nutrition and Metabolic Syndrome Management", which included a series of articles about the role of bioactive compounds, amino acids/proteins and fatty acids for personalized nutritional applications [...].

The regulation of inflammation-related genes after palmitic acid and DHA treatments is not mediated by DNA methylation.

Fatty acids (FAs) are known to participate in body inflammatory responses. In particular, saturated FAs such as palmitic acid (PA) induce inflammatory signals in macrophages, whereas polyunsaturated FAs, including docosahexaenoic acid (DHA), have been related to anti-inflammatory effects. Several studies have suggested a role of fatty acids on DNA methylation, epigenetically regulating gene expression in inflammation processes. Therefore, this study investigated the effect of PA and DHA on the inflammation-related genes on human macrophages. In addition, a second aim was to study the epigenetic mechanism underlying the effect of FAs on the inflammatory response. For these purposes, human acute monocytic leukaemia cells (THP-1) were differentiated into macrophages with 12-O-tetradecanoylphorbol-13-acetate (TPA), followed by an incubation with PA or DHA. At the end of the experiment, mRNA expression, protein secretion, and CpG methylation of the following inflammatory genes were analysed: interleukin 1 beta (IL1B), tumour necrosis factor (TNF), plasminogen activator inhibitor-1 (SERPINE1) and interleukin 18 (IL18). The results showed that the treatment with PA increased IL-18 and TNF-α production. Contrariwise, the supplementation with DHA reduced IL-18, TNF-α and PAI-1 secretion by macrophages. However, the incubation with these fatty acids did not apparently modify the DNA methylation status of the investigated genes in the screened CpG sites. This research reveals that PA induces important pro-inflammatory markers in human macrophages, whereas DHA decreases the inflammatory response. Apparently, DNA methylation is not directly involved in the fatty acid-mediated regulation of the expression of these inflammation-related genes.

Low doses of cocoa extract supplementation ameliorate diet-induced obesity and insulin resistance in rats.

Cocoa polyphenols exhibit high antioxidant activity and have been proposed as a potential adjuvant for the treatment of metabolic disturbances. Here, we demonstrate that supplementation with low doses (14 and 140 mg per kg per rat) of a complete cocoa extract induces metabolic benefits in a diet-induced obesity (DIO) model of Wistar rats. After 10 weeks, cocoa extract-supplemented animals exhibited significantly lower body weight gain and food efficiency, with no differences in energy intake. Cocoa significantly reduced visceral (epididymal and retroperitoneal) and subcutaneous fat accumulation accompanied by a significant reduction in the adipocyte size, which was mediated by downregulation of the adipocyte-specific genes Cebpa, Fasn and Adipoq. Additionally, cocoa extract supplementation reduced the triacylglycerol/high density lipoprotein (TAG/HDL) ratio, decreased hepatic triglyceride accumulation, improved insulin sensitivity by reducing HOMA-IR, and significantly ameliorated glucose tolerance after an intraperitoneal glucose tolerance test. Finally, no adverse effect was observed in an in vivo toxicity evaluation of our cocoa extract at doses up to 500 mg kg-1 day-1. Our data demonstrate that low doses of cocoa extract supplementation (14 and 140 mg kg-1 day-1) are safe and sufficient to counteract obesity and type-2 diabetes in rats and provide new insights into the potential application of cocoa supplements in the management of the metabolic syndrome.

Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation.

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

Quality of Dietary Fat Intake and Body Weight and Obesity in a Mediterranean Population: Secondary Analyses within the PREDIMED Trial.

A moderately high-fat Mediterranean diet does not promote weight gain. This study aimed to investigate the association between dietary intake of specific types of fat and obesity and body weight. A prospective cohort study was performed using data of 6942 participants in the PREDIMED trial, with yearly repeated validated food-frequency questionnaires, and anthropometric outcomes (median follow-up: 4.8 years). The effects of replacing dietary fat subtypes for one another, proteins or carbohydrates were estimated using generalized estimating equations substitution models. Replacement of 5% energy from saturated fatty acids (SFA) with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) resulted in weight changes of -0.38 kg (95% Confidece Iinterval (CI): -0.69, -0.07), and -0.51 kg (95% CI: -0.81, -0.20), respectively. Replacing proteins with MUFA or PUFA decreased the odds of becoming obese. Estimates for the daily substitution of one portion of red meat with white meat, oily fish or white fish showed weight changes up to -0.87 kg. Increasing the intake of unsaturated fatty acids at the expense of SFA, proteins, and carbohydrates showed beneficial effects on body weight and obesity. It may therefore be desirable to encourage high-quality fat diets like the Mediterranean diet instead of restricting total fat intake.

Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and Skeletal Muscle Depend on Feeding Conditions?

The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided into four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy-restricted group and an energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius muscle and fat depots were measured. Activities of carnitine palmitoyltransferase (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3), uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome proliferator-activated receptor (PPARα) and AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC1α) activation were measured. No changes in IBAT and gastrocnemius weights were found. Energy-restriction, but not resveratrol, decreased the weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating the SIRT1/PGC1α/PPARα axis. Resveratrol also induced fatty acid oxidation and glucose uptake. These effects were similar when resveratrol was combined with energy restriction. In the case of gastrocnemius muscle, the effects were not as clear as in the case of IBAT. In this tissue, resveratrol increased oxidative capacity. The combination of resveratrol and energy restriction seemingly did not improve the effects induced by the polyphenol alone.

Borago officinalis seed oil (BSO), a natural source of omega-6 fatty acids, attenuates fat accumulation by activating peroxisomal beta-oxidation both in C. elegans and in diet-induced obese rats.

Obesity is a medical condition with increasing prevalence, characterized by an accumulation of excess fat that could be improved using some bioactive compounds. However, many of these compounds with in vitro activity fail to respond in vivo, probably due to the sophistication of the physiological energy regulatory networks. In this context, C. elegans has emerged as a plausible model for the identification and characterization of the effect of such compounds on fat storage in a complete organism. However, the results obtained in such a simple model are not easily extrapolated to more complex organisms such as mammals, which hinders its application in the short term. Therefore, it is necessary to obtain new experimental data about the evolutionary conservation of the mechanisms of fat loss between worms and mammals. Previously, we found that some omega-6 fatty acids promote fat loss in C. elegans by up-regulation of peroxisomal fatty acid ß-oxidation in an omega-3 independent manner. In this work, we prove that the omega-6 fatty acids' effects on worms are also seen when they are supplemented with a natural omega-6 source (borage seed oil, BSO). Additionally, we explore the anti-obesity effects of two doses of BSO in a diet-induced obesity rat model, validating the up-regulation of peroxisomal fatty acid ß-oxidation. The supplementation with BSO significantly reduces body weight gain and energy efficiency and prevents white adipose tissue accumulation without affecting food intake. Moreover, BSO also increases serum HDL-cholesterol levels, improves insulin resistance and promotes the down-regulation of Cebpa, an adipogenesis-related gene. Therefore, we conclude that the effects of omega-6 fatty acids are highly conserved between worms and obesity-induced mammals, so these compounds could be considered to treat or prevent obesity-related disorders.

Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.

BACKGROUND: Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). METHODS: This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. RESULTS: Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation. CONCLUSIONS: This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01138774 .