Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies.

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

Bacillus coagulans GBI-30, 6086 (BC30) improves lactose digestion in rats exposed to a high-lactose meal.

PURPOSE: Bacillus coagulans GBI-30, 6086 (BC30) was previously shown to improve nutrient digestibility and amino acid absorption from milk protein in vitro. However, the effect of supplementation with this probiotic on lactose digestibility has not yet been evaluated in vivo. METHODS: Wistar female rats were exposed to an acute high-lactose diet (LD; 35% lactose) meal challenge after 7 days of administration of BC30 (LD-BC; n = 10) or vehicle (LD-C; n = 10). Rats treated with vehicle and exposed to control diet (CD; 35% corn starch) meal were used as controls (CD-C; n = 10). Carbohydrate oxidation (CH_OX) and lipid oxidation (L_OX) were monitored by indirect calorimetry before and after lactose challenge. After the challenge, rats were treated daily with vehicle or probiotic for an additional week and were fed with CD or LD ad libitum to determine the effects of BC30 administration in a lactose-induced diarrhoea and malnutrition model. RESULTS: LD-C rats showed lower CH_OX levels than CD rats, while LD-BC rats showed similar CH_OX levels compared to CD rats during the lactose challenge, suggesting a better digestion of lactose in the rats supplemented with BC30. BC30 completely reversed the increase in the small intestine length of LD-C animals. LD-BC rats displayed increased intestinal mRNA Muc2 expression. No significant changes were observed due to BC30 administration in other parameters, such as serum calprotectin, intestinal MPO activity, intestinal A1AT and SGLT1 levels or intestinal mRNA levels of Claudin2 and Occludin. CONCLUSION: Treatment with BC30 improved the digestibility of lactose in an acute lactose challenge and ameliorated some of the parameters associated with lactose-induced malnutrition.

Pomegranate natural extract Pomanox® positively modulates skin health-related parameters in normal and UV-induced photoaging conditions in Hs68 human fibroblast cells.

Skin photoaging is primarily caused by ultraviolet radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyperpigmentation and skin elasticity loss. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and antiaging properties. Here, we evaluated the effects of the pomegranate natural extract Pomanox® on skin health-related parameters in normal and UV-induced photoaging conditions in human fibroblast Hs68 cells. Moreover, the inhibitory effects of Pomanox® on tyrosinase activity were assessed. In normal conditions, Pomanox® significantly modulated collagen and hyaluronic acid metabolisms. In UV-exposed cells, both preventive and regenerative treatments with Pomanox® positively modulated hyaluronic acid metabolism and decreased ROS levels. However, only the preventive treatment modulated collagen metabolism. Finally, Pomanox® showed a marked inhibitory capacity of tyrosinase activity (IC50 = 394.7 µg/mL). The modulation of skin health-related parameters exhibited by Pomanox® open a wide range of potential applications of this product.

Brain N-Glycosylation and Lipidomic Profile Changes Induced by a High-Fat Diet in Dyslipidemic Hamsters.

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.

Mediterranean natural extracts improved cognitive behavior in zebrafish and healthy rats and ameliorated lps-induced cognitive impairment in a sex dependent manner.

BACKGROUND: Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer's disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. RESULTS: Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. CONCLUSIONS: We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.

Effects of enriched seafood sticks (heat-inactivated B. animalis subsp. lactis CECT 8145, inulin, omega-3) on cardiometabolic risk factors and gut microbiota in abdominally obese subjects: randomized controlled trial.

PURPOSE: To assess the effects of enriched seafood sticks with postbiotic and bioactive compounds on CMD risk factors and the gut microbiota in abdominally obese individuals. METHODS: Randomized, double-blind, parallel, placebo-controlled trial with abdominally obese individuals. Participants (n = 120) consumed 50 g/day of enriched seafood sticks containing SIAP: (1010 colony forming units (CFUs) of heat-inactivated B. animalis subsp. lactis CECT8145, 370 mg/day omega 3 and 1.7 g/day inulin), or 50 g/day of placebo seafood sticks for 12 weeks. At 12 weeks, an acute single-dose study of 4 h was performed. RESULTS: Sustained SIAP2 consumption significantly decreased the insulin by - 5.25 mg/dL and HOMA-IR (homeostatic Model Assessment of Insulin Resistance) by - 1.33. In women, SIAP2 consumption significantly decreased the pulse pressure (PP) by - 4.69 mmHg. Gut microbiota analysis showed a negative association between glycemic parameter reduction and Alistipes finegoldii and Ruminococcaceae, and between PP reduction and Prevotella 9-ASV0283 and Christensenellaceae. In the acute single dose-study 4-h, SIAP2 consumption produced a lower increase in the postprandial circulating triglyceride levels [23.9 (7.03) mg/dL (mean [standard error])] than the observed with placebo [49.0 (9.52)] mg/dL. CONCLUSION: In abdominally obese individuals, enriched seafood sticks induce a potential protection against type 2 diabetes development by the reduction in the insulin and HOMA-IR; and in cardiovascular disease, in women, by the PP reduction. These effects are accompanied by partial changes in the gut microbiota composition. The enriched seafood sticks reduce the atherogenic triglyceride postprandial concentrations. Our results support the use of enriched seafood sticks as a complementary strategy in the management of CMD risk factors. REGISTRATION NUMBER OF CLINICAL TRIAL: ( www. CLINICALTRIALS: gov ): NCT03630588 (August 15, 2018).

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging.

Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of "omic" technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.

Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors.

Obesity is an epidemic disease worldwide, characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. To improve this situation, a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) was assessed as a promising treatment in a high-fat diet (HFD) mouse model. Obese animals were distributed into two groups, orally treated with the vehicle (obese + vehicle) or with the combination of metabolic cofactors (obese + MC) for 4 weeks. Body and adipose depots weights; insulin and glucose tolerance tests; indirect calorimetry; and thermography assays were performed at the end of the intervention. Histological analysis of epidydimal white adipose tissue (EWAT) and brown adipose tissue (BAT) was carried out, and the expression of key genes involved in both fat depots was characterized by qPCR. We demonstrated that MC supplementation conferred a moderate reduction of obesity and adiposity, an improvement in serum glucose and lipid metabolic parameters, an important improvement in lipid oxidation, and a decrease in adipocyte hypertrophy. Moreover, MC-treated animals presented increased adipose gene expression in EWAT related to lipolysis and fatty acid oxidation. Furthermore, MC supplementation reduced glucose intolerance and insulin resistance, with an increased expression of the glucose transporter Glut4; and decreased fat accumulation in BAT, raising non-shivering thermogenesis. This treatment based on a specific combination of metabolic cofactors mitigates important pathophysiological characteristics of obesity, representing a promising clinical approach to this metabolic disease.

Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats.

Chronic inflammation is an important risk factor in a broad variety of physical and mental disorders leading to highly prevalent non-communicable diseases (NCDs). However, there is a need for a deeper understanding of this condition and its progression to the disease state. For this reason, it is important to define metabolic pathways and complementary biomarkers associated with homeostatic disruption in chronic inflammation. To achieve that, male Wistar rats were subjected to intraperitoneal and intermittent injections with saline solution or increasing lipopolysaccharide (LPS) concentrations (0.5, 5 and 7.5 mg/kg) thrice a week for 31 days. Biochemical and inflammatory parameters were measured at the end of the study. To assess the omics profile, GC-qTOF and UHPLC-qTOF were performed to evaluate plasma metabolome; 1H-NMR was used to evaluate urine metabolome; additionally, shotgun metagenomics sequencing was carried out to characterize the cecum microbiome. The chronicity of inflammation in the study was evaluated by the monitoring of monocyte chemoattractant protein-1 (MCP-1) during the different weeks of the experimental process. At the end of the study, together with the increased levels of MCP-1, levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) along with 8-isoprostanes (an indicative of oxidative stress) were significantly increased (p-value < 0.05). The leading features implicated in the current model were tricarboxylic acid (TCA) cycle intermediates (i.e., alpha-ketoglutarate, aconitic acid, malic acid, fumaric acid and succinic acid); lipids such as specific cholesterol esters (ChoEs), lysophospholipids (LPCs) and phosphatidylcholines (PCs); and glycine, as well as N, N-dimethylglycine, which are related to one-carbon (1C) metabolism. These metabolites point towards mitochondrial metabolism through TCA cycle, ß-oxidation of fatty acids and 1C metabolism as interconnected pathways that could reveal the metabolic effects of chronic inflammation induced by LPS administration. These results provide deeper knowledge concerning the impact of chronic inflammation on the disruption of metabolic homeostasis.

Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors' Combination.

The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors' combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.

Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).

PURPOSE: To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals. METHODS: In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose-response studies were performed at baseline and after 12 weeks. RESULTS: A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes related to hypertension (PTX3, NLRP3, NPSR1 and NAMPT) were differentially expressed in peripheral blood mononuclear cells (P < 0.05). CONCLUSION: Hesperidin in OJ reduces SBP and PP after sustained consumption, and after a single dose, the chronic consumption of EOJ enhances its postprandial effect. Decreases in systemic and transcriptomic biomarkers were concomitant with BP and PP changes. EOJ could be a useful co-adjuvant tool for BP and PP management in pre- and stage-1 hypertensive individuals.

A restricted cafeteria diet ameliorates biometric and metabolic profile in a rat diet-induced obesity model.

The administration of anti-obesity bioactive compounds and/or functional foods in rodents fed energy restriction diets based on chow food can be difficult to interpret. We propose an energy restricted cafeteria (CAF) diet as a dietetic intervention to be combined with other therapies. Postweaning male rats were fed standard chow, CAF diet or 30% energy restricted CAF diet (CAF-R) for 8 weeks. The CAF-R diet lowered energy intake and the increase of body weight and body mass index due to the CAF diet, lead to an intermediate feed efficiency, and dampened the CAF diet-induced alterations on body composition, serum levels of triacylglycerides and NEFAs, and insulin resistance. These effects were associated with diminished Ucp1, Nrf1 and Tfam1 gene expression in brown adipose tissue. In conclusion, the CAF-R diet ameliorated obesity and related metabolic disorders induced by a regular CAF diet, turning it in a useful tool to study anti-obesity compounds.

Alterations in Metabolome and Microbiome Associated with an Early Stress Stage in Male Wistar Rats: A Multi-Omics Approach.

Stress disorders have dramatically increased in recent decades becoming the most prevalent psychiatric disorder in the United States and Europe. However, the diagnosis of stress disorders is currently based on symptom checklist and psychological questionnaires, thus making the identification of candidate biomarkers necessary to gain better insights into this pathology and its related metabolic alterations. Regarding the identification of potential biomarkers, omic profiling and metabolic footprint arise as promising approaches to recognize early biochemical changes in such disease and provide opportunities for the development of integrative candidate biomarkers. Here, we studied plasma and urine metabolites together with metagenomics in a 3 days Chronic Unpredictable Mild Stress (3d CUMS) animal approach that aims to focus on the early stress period of a well-established depression model. The multi-omics integration showed a profile composed by a signature of eight plasma metabolites, six urine metabolites and five microbes. Specifically, threonic acid, malic acid, alpha-ketoglutarate, succinic acid and cholesterol were proposed as key metabolites that could serve as key potential biomarkers in plasma metabolome of early stages of stress. Such findings targeted the threonic acid metabolism and the tricarboxylic acid (TCA) cycle as important pathways in early stress. Additionally, an increase in opportunistic microbes as virus of the Herpesvirales was observed in the microbiota as an effect of the primary stress stages. Our results provide an experimental biochemical characterization of the early stage of CUMS accompanied by a subsequent omic profiling and a metabolic footprinting that provide potential candidate biomarkers.

Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial.

BACKGROUND: The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown. OBJECTIVE: To assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers. DESIGN: Randomized, parallel, double-blind, placebo-controlled trial with abdominally obese individuals. Participants (n = 135) consumed 1 capsule/day containing 1010 colony forming unit (CFU) of Ba8145, 1010 CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months. RESULTS: Ba8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003). CONCLUSIONS: In abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.

Hepatic accumulation of S-adenosylmethionine in hamsters with non-alcoholic fatty liver disease associated with metabolic syndrome under selenium and vitamin E deficiency.

Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high-fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT. SAM plays a key role in the maintenance of cellular homeostasis and cell cycle control. In agreement, analysis of over-represented transcription factors revealed a central role of c-myc and c-Jun pathways accompanied by negative correlations between SAM concentration, MYC expression and AMPK phosphorylation. These findings point to a drift of cell cycle control toward senescence in livers of HFD animals, which could explain the onset of NASH in this model. In contrast, hamsters with NAFLD induced by a conventional high-fat diet did not show SAM accumulation, suggesting a key role of selenium and vitamin E in SAM homeostasis. In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation.

Differential effects of habitual chow-based and semi-purified diets on lipid metabolism in lactating rats and their offspring.

Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (5·08 and 3·26 %, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15 %, respectively), and cholesterol (26 and 69 mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.

Long-term intake of soyabean phytosterols lowers serum TAG and NEFA concentrations, increases bile acid synthesis and protects against fatty liver development in dyslipidaemic hamsters.

Various human trials and pre-clinical studies have suggested that dietary plant sterols possess hypotriacylglycerolaemic properties apart from their cholesterol-lowering properties. We hypothesised that phytosterols (PS) might attenuate triacylglycerolaemia by interfering with the deleterious effects of cholesterol overload in the liver. In the present study, twenty hamsters (Mesocricetus auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel, a healthy group was fed a standard diet (n 10). PS normalised fasting plasma cholesterol concentrations completely after 20 d and were also able to normalise serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular steatosis and impaired the expression of key genes related to fatty acid oxidation such as PPARA, carnitine palmitoyltransferase-Iα (CPT1A) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely protected against HFD-induced steatosis and resulted in a normalised hepatic gene expression profile. The protection of the hepatic function by PS was paralleled by increased faecal cholesterol excretion along with a 2-fold increase in the biliary bile acid (BA):cholesterol ratio. The present study supports the conclusion that long-term consumption of PS can reduce serum TAG and NEFA concentrations and can protect against the development of fatty liver via different mechanisms, including the enhancement of BA synthesis. The results of the present study place these compounds as promising hepatoprotective agents against fatty liver and its derived pathologies.

Combined supplementation with hesperidin, phytosterols and curcumin decreases adiposity and improves metabolic health in ovariectomized rats.

In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17ß-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Lpl and Cd36 in MWAT. These results were very similar to those observed in OVX-E2 animals. OVX-MI rats also displayed a higher lean body mass, lean/fat mass ratio, adiponectin-to-leptin ratio and insulin sensitivity than their OVX counterparts. Our findings can pave the way for using this MI formulation as an alternative therapy to manage obesity and to improve the cardiometabolic health of menopausal women.

A single-blinded, randomized, parallel intervention to evaluate genetics and omics-based personalized nutrition in general population via an e-commerce tool: The PREVENTOMICS e-commerce study.

BACKGROUND: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status. OBJECTIVES: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population. METHODS: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits. RESULTS: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control-3 points; 95% confidence interval [CI]: 2.2, 3.8; PN-2.7 points; 95% CI: 2.0, 3.3; and PP-2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (ß: -0.37; 95% CI: -0.56, -0.18), oxidative stress (ß: -0.37; 95% CI: -0.60, -0.15), microbiota (ß: -0.38; 95% CI: -0.63, -0.15), and inflammation (ß: -0.78; 95% CI: -1.24, -0.31) compared with control diet. CONCLUSIONS: Integration of personalized strategies within an e-commerce-like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN. This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).

Peripheral blood mononuclear cells: a potential source of homeostatic imbalance markers associated with obesity development.

Peripheral blood mononuclear cells (PBMC) have a great potential for nutrition and obesity studies. PBMC reflect the nutritional response of key organs involved in energy homeostasis maintenance, which is altered in the obese state. Here, we aimed to determine the usefulness of PBMC as a source of early markers of obesity. To that purpose, we analysed whether PBMC could reflect the insensitivity to changes in feeding conditions associated with obesity during the development of this pathology. Expression of key genes central to energy metabolism was measured by Q-PCR in PBMC samples of normoweight (control) and cafeteria-fed (obese) rats in feeding, fasting and refeeding conditions. Samples were obtained monthly from 2 (beginning of cafeteria diet-feeding) to 6 months of age. In general terms, expression of genes related to fatty acid synthesis (Fasn, Srebp1) and adipogenesis (Pparg) decreased with fasting and increased with refeeding. Conversely, the expression of a key gene regulating beta-oxidation (Cpt1a) and the gene for an orexigenic neuropeptide (Npy)-in accordance with their metabolic role-increased with fasting and decreased with refeeding. This expression pattern disappeared in obese rats, in which insensitivity to feeding conditions was observed after only 1 month of cafeteria diet-feeding. Thus, during development, PBMC accurately reflect nutritional regulation of energy homeostasic genes and the insensitivity to feeding associated with obesity, even in the earlier stages with a low degree of overweight. For this reason, this set of blood cells could constitute a potential source of biomarkers of early homeostatic imbalance which would be useful in nutrition studies that could help prevent the occurrence of obesity.