Mediterranean Diet Combined with Regular Aerobic Exercise and Hemp Protein Supplementation Modulates Plasma Circulating Amino Acids and Improves the Health Status of Overweight Individuals.

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO's recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (-54.0%), and TAG levels (-49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.

Mediterranean Diet and Melatonin: A Systematic Review.

The Mediterranean diet (MD) has beneficial effects on human health, which is evidenced by the observation of lower incidence rates of chronic diseases in Mediterranean countries. The MD dietary pattern is rich in antioxidants, such as melatonin, which is a hormone produced mainly by the pineal gland and controls several circadian rhythms. Additionally, melatonin is found in foods, such as fruit and vegetables. The purpose of this systematic review was to assess the melatonin content in Mediterranean foods and to evaluate the influence of the MD on melatonin levels in both humans and model organisms. A comprehensive search was conducted in four databases (PubMed, Scopus, Cochrane Library and Web of Science) and data were extracted. A total of 31 records were chosen. MD-related foods, such as tomatoes, olive oil, red wine, beer, nuts, and vegetables, showed high melatonin contents. The consumption of specific MD foods increases melatonin levels and improves the antioxidant status in plasma.

Modulation of Beta-Amyloid-Activated Primary Human Neutrophils by Dietary Phenols from Virgin Olive Oil.

The defense mechanism against harmful stimuli is inflammation. Indeed, neurodegenerative disorders can arise as a result of a persistent neuroinflammation. Beta-amyloid (Aß1-42) is an early trigger in the origination of Alzheimer's disease, leading to synaptic and cognitive impairments. Virgin olive oil (VOO) is correlated with a decreased risk of developing immune-inflammatory disorders, but the potential effects of the phenolic fraction (PF) from VOO in the modulation of neuroinflammatory processes in neutrophils remain unknown. In this study, we investigated the ability of the PF to modulate the activation of Aß1-42-stimulated primary human neutrophils, focusing on the expression of gene and surface markers and the release of pro-inflammatory and chemoattractant mediators. Down-regulation of pro-inflammatory cytokine gene expression in Aß1-42-treated neutrophils, among other changes, was reported. Furthermore, pretreatment with PF prevented neutrophil activation. The beneficial effects in the modulation of inflammatory responses show the relevance of VOO to achieve a healthier diet that can help prevent inflammatory diseases.

Lipoprotein Metabolism, Protein Aggregation, and Alzheimer's Disease: A Literature Review.

Alzheimer's disease (AD) is the most common form of dementia. The physiopathology of AD is well described by the presence of two neuropathological features: amyloid plaques and tau neurofibrillary tangles. In the last decade, neuroinflammation and cellular stress have gained importance as key factors in the development and pathology of AD. Chronic cellular stress occurs in degenerating neurons. Stress Granules (SGs) are nonmembranous organelles formed as a response to stress, with a protective role; however, SGs have been noted to turn into pathological and neurotoxic features when stress is chronic, and they are related to an increased tau aggregation. On the other hand, correct lipid metabolism is essential to good function of the brain; apolipoproteins are highly associated with risk of AD, and impaired cholesterol efflux and lipid transport are associated with an increased risk of AD. In this review, we provide an insight into the relationship between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.

Proteomic analysis of postprandial high-density lipoproteins in healthy subjects.

The relationship between the functionality and composition of high-density lipoproteins (HDL) is yet not fully studied, and little is known about the influence of the diet in HDL proteome. Therefore, the aim of this research was to elucidate the HDL proteome associated to postprandial hyperlipidemia. Male volunteers were recruited for an interventional study with high fatty acid-based meals. Blood samples were collected before the intake (baseline), and 2-3 (postprandial peak) and 5-6 (postprandial post peak) hours later. HDL were purified and the protein composition was quantified by LC-MS/MS. Statistical analysis was performed by lineal models (amica) and by ANOVA and multi-t-test of the different conditions (MetaboAnalyst). Additionally, a clustering of the expression profiles of each protein was done with coseq R package (RStudio). Initially, 320 proteins were identified but only 119 remained after the filtering. APOM, APOE, APOB, and APOA2, proteins previously identified in the HDL proteome, were the only proteins with a statistically significant altered expression in postprandial hyperlipidemia when compared to baseline (p values <0.05 and logFC >1). In conclusion, we have been able to describe several behaviors of the whole HDL proteome during the postprandial hyperlipidemic metabolism.

Kiwicha (Amaranthus caudatus L.) protein hydrolysates reduce intestinal inflammation by modulating the NLRP3 inflammasome pathway.

The increase in the world population along with new policies aimed at a more sustainable world has led to the need of searching for new food sources, which are environmentally friendly, implying healthy and nutritious diets. This study explored the biological activity of two kiwicha (Amaranthus caudatus L.) protein hydrolysates obtained with the aid of Bioprotease LA-660 regarding their anti-inflammatory response at the intestinal level, employing the CACO-2 cell line. The results obtained showed that the in vitro administration of these hydrolysates decreased the expression of proinflammatory cytokines, increased the expression of anti-inflammatory cytokines, and decreased the gene expression of the major components of inflammasomes in the intestinal CACO-2 cell model. To the best of our knowledge, this is the first study involving the evaluation of the anti-inflammatory activity of kiwicha hydrolysates at the intestinal level, employing the CACO-2 cell model and its ultrastructural characterization using scanning electron microscopy. We conclude that the Amaranthus caudatus hydrolysates are a valuable source of active peptides that take part as functional ingredients in food and nutraceutical preparations.

Acyclic Diterpene Phytol from Hemp Seed Oil (Cannabis sativa L.) Exerts Anti-Inflammatory Activity on Primary Human Monocytes-Macrophages.

Seeds from non-drug varieties of hemp (Cannabis sativa L.) have been used for traditional medicine, food, and fiber production. Our study shows that phytol obtained from hemp seed oil (HSO) exerts anti-inflammatory activity in human monocyte-macrophages. Fresh human monocytes and human macrophages derived from circulating monocytes were used to evaluate both plasticity and anti-inflammatory effects of phytol from HSO at 10-100 mM using FACS analysis, ELISA, and RT-qPCR methods. The quantitative study of the acyclic alcohol fraction isolated from HSO shows that phytol is the most abundant component (167.59 ± 1.81 mg/Kg of HSO). Phytol was able to skew monocyte-macrophage plasticity toward the anti-inflammatory non-classical CD14+CD16++ monocyte phenotype and toward macrophage M2 (CD200Rhigh and MRC-1high), as well as to reduce the production of IL-1ß, IL-6, and TNF-α, diminishing the inflammatory competence of mature human macrophages after lipopolysaccharide (LPS) treatment. These findings point out for the first time the reprogramming and anti-inflammatory activity of phytol in human monocyte-macrophages. In addition, our study may help to understand the mechanisms by which phytol from HSO contributes to the constant and progressive plasticity of the human monocyte-macrophage linage.

Antioxidant and Immunomodulatory Properties of Chia Protein Hydrolysates in Primary Human Monocyte-Macrophage Plasticity.

Chia (Salvia hispanica L.) seed has high potential in the development of functional food due to its protein content with a special amino acid profile. Among the hematopoietic-derived cells, monocytes are endowed with high plasticity, responsible for their pro- and anti-inflammatory function in M1 and M2 phenotype polarization, respectively. Indeed, monocytes are involved in several oxidative- and inflammatory-associated disorders such as cancer, obesity, and cardiovascular and neurodegenerative diseases. This study was designed to investigate the role of chia protein hydrolysates (CPHs) in primary human monocyte-macrophage plasticity response using biochemical, RT-qPCR, and ELISA assays. Our results showed that CPHs reduce ROS and nitrite output, as pro-inflammatory cytokine secretion, and enhance the expression and release of anti-inflammatory cytokines. In addition, CPHs reverse LPS-associated M1 polarization into M2. These findings open new opportunities for developing nutritional strategies with chia as a dietary source of biopeptides to prevent the development and progression of oxidative- and inflammatory-related diseases.

High-density lipoproteins and immune response: A review.

High-density lipoproteins (HDLs) are heterogeneous lipoproteins that modify their composition and functionality depending on physiological or pathological conditions. The main roles of HDL are cholesterol efflux, and anti-inflammatory and antioxidant functions. These functions can be compromised under pathological conditions. HDLs play a role in the immune system as anti-inflammatory molecules but when inflammation occurs, HDLs change their composition and carry pro-inflammatory cargo. Hence, many molecular intermediates that influence inflammatory microenvironments and cell signaling pathways can modulate HDLs structural modification and function. This review provides a comprehensive assessment of the importance of HDL composition and anti-inflammatory function in the onset and progression of atherosclerotic cardiovascular diseases. On the other hand, immune cell activation during progression of atheroma plaque formation can be influenced by HDLs through HDL-derived cholesterol depletion from lipid rafts and through HDL interaction with HDL receptors expressed on T and B lymphocytes. Cholesterol efflux is mediated by HDL receptors located in lipid rafts in peripheral cells, which undergo membrane structural modifications, and interferes with subsequent molecules interactions or intracellular signaling cascades. Regarding antigen-presentation cells such as macrophages or dendritic cells, HDL function may then modulate lymphocytes activation in immune response. Our review also contributes to the understanding of the effects exerted by HDLs in signal transduction associated to our immune cell population during chronic diseases progression.

Obesity-Associated Metabolic Disturbances Reverse the Antioxidant and Anti-Inflammatory Properties of High-Density Lipoproteins in Microglial Cells.

High-density lipoproteins (HDLs) play an important role in reverse cholesterol transport and present antioxidant properties, among others. In the central nervous system (CNS), there are HDLs, where these lipoproteins could influence brain health. Owing to the new evidence of HDL functionality remodeling in obese patients, and the fact that obesity-associated metabolic disturbances is pro-inflammatory and pro-oxidant, the aim of this study was to investigate if HDL functions are depleted in obese patients and obesity-associated microenvironment. HDLs were isolated from normal-weight healthy (nwHDL) and obese men (obHDL). The oxHDL level was measured by malondialdehyde and 4-hydroxynoneal peroxided products. BV2 microglial cells were exposed to different concentrations of nwHDL and obHDL in different obesity-associated pro-inflammatory microenvironments. Our results showed that hyperleptinemia increased oxHDL levels. In addition, nwHDLs reduced pro-inflammatory cytokines' release and M1 marker gene expression in BV2 microglial cells. Nevertheless, both nwHDL co-administered with LPS+leptin and obHDL promoted BV2 microglial activation and a higher pro-inflammatory cytokine production, thus confirming that obesity-associated metabolic disturbances reverse the antioxidant and anti-inflammatory properties of HDLs in microglial cells.

High-Density Lipoproteins and Mediterranean Diet: A Systematic Review.

Cardiovascular disease (CVD) is the leading cause of global mortality and the study of high-density lipoproteins (HDL) particle composition and functionality has become a matter of high interest, particularly in light to the disappointing clinical data for HDL-cholesterol (HDL-C) raising therapies in CVD secondary prevention and the lack of association between HDL-C and the risk of CVD. Recent evidences suggest that HDL composition and functionality could be modulated by diet. The purpose of this systematic review was to investigate the effect of Mediterranean diet (MD) on changes in HDL structure and functionality in humans. A comprehensive search was conducted in four databases (PubMed, Scopus, Cochrane library and Web of Science) and 13 records were chosen. MD showed favorable effects on HDL functionality, particularly by improving HDL cholesterol efflux capacity and decreasing HDL oxidation. In addition, HDL composition and size were influenced by MD. Thus, MD is a protective factor against CVD associated with the improvement of HDL quality and the prevention of HDL dysfunctionality.

Dietary Fatty Acids in Postprandial Triglyceride-Rich Lipoproteins Modulate Human Monocyte-Derived Dendritic Cell Maturation and Activation.

Dietary fatty acids have been demonstrated to modulate systemic inflammation and induce the postprandial inflammatory response of circulating immune cells. We hypothesized that postprandial triglyceride-rich lipoproteins (TRLs) may have acute effects on immunometabolic homeostasis by modulating dendritic cells (DCs), sentinels of the immunity that link innate and adaptive immune systems. In healthy volunteers, saturated fatty acid (SFA)-enriched meal raised serum levels of granulocyte/macrophage colony-stimulating factor GM-CSF (SFAs > monounsaturated fatty acids (MUFAs) = polyunsaturated fatty acids (PUFAs)) in the postprandial period. Autologous TRL-SFAs upregulated the gene expression of DC maturation (CD123 and CCR7) and DC pro-inflammatory activation (CD80 and CD86) genes while downregulating tolerogenic genes (PD-L1 and PD-L2) in human monocyte-derived DCs (moDCs). These effects were reversed with oleic acid-enriched TRLs. Moreover, postprandial SFAs raised IL-12p70 levels, while TRL-MUFAs and TRL-PUFAs increased IL-10 levels in serum of healthy volunteers and in the medium of TRL-treated moDCs. In conclusion, postprandial TRLs are metabolic entities with DC-related tolerogenic activity, and this function is linked to the type of dietary fat in the meal. This study shows that the intake of meals enriched in MUFAs from olive oil, when compared with meals enriched in SFAs, prevents the postprandial production and priming of circulating pro-inflammatory DCs, and promotes tolerogenic response in healthy subjects. However, functional assays with moDCs generated in the presence of different fatty acids and T cells could increase the knowledge of postprandial TRLs' effects on DC differentiation and function.

Grape (Vitis vinifera L.) Seed Oil: A Functional Food from the Winemaking Industry.

Wine production is an ancient human activity that generates several by-products, which include some constituents known for their potential in health care and for their role in the food or cosmetic industries. Any variety of grape (Vitis vinifera L.) contains nutrients and bioactive compounds available from their juice or solid parts. Grape seed extract has demonstrated many activities in disease prevention, such as antioxidant effects, which make it a potential source of nutraceuticals. Grape seed is a remarkable winery industry by-product due to the bioactivity of its constituents. Methods for recovery of oil from grape seeds have evolved to improve both the quantity and quality of the yield. Both the lipophilic and hydrophilic chemicals present in the oil of V. vinifera L. make this wine by-product a source of natural nutraceuticals. Food and non-food industries are becoming novel targets of oil obtained from grape seeds given its various properties. This review focuses on the advantages of grape seed oil intake in our diet regarding its chemical composition in industries not related to wine production and the economic and environmental impact of oil production.

Hemp (Cannabis sativa L.) Protein Hydrolysates Promote Anti-Inflammatory Response in Primary Human Monocytes.

Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide (LPS)-activated primary human monocytes. CD14+ cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate (HPI) and hydrolysates (HPHs) was evaluated on LPS-stimulated human primary monocytes. The specific markers of inflammation, polarization, and chemoattraction were measured by RT-qPCR and ELISA assays. Our results showed that HPPs decreased the pro-inflammatory mediators (TNFα, IL-1ß, and IL-6) and increased the anti-inflammatory mediators (IL-10 and IL-4). In addition, M1 polarization marker gene expression (CCR7 and iNOS) was downregulated by HPPs and, M2 polarization marker gene expression (CD200R and MRC1) was upregulated. Finally, the mRNA expression of chemotaxis genes (CCR2 and CCL2) was downregulated by HPPs. In conclusion, this study suggests that HPPs may improve chronic inflammatory states and promote regenerative processes by reprogramming monocytes toward M2 polarization phenotype.

A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice.

Bioactive peptides are related to the prevention and treatment of many diseases. GPETAFLR is an octapeptide that has been isolated from lupine (Lupinus angustifolius L.) and shows anti-inflammatory properties. The aim of this study was to evaluate the potential activity of GPETAFLR to prevent non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD)-induced obese mice. C57BL/6J mice were fed a standard diet or HFD. Two of the groups fed the HFD diet were treated with GPETAFLR in drinking water at 0.5 mg kg-1 day-1 or 1 mg kg-1 day-1. To determine the ability of GPETAFLR to improve the onset and progression of non-alcoholic fatty liver disease, histological studies, hepatic enzyme profiles, inflammatory cytokine and lipid metabolism-related genes and proteins were analysed. Our results suggested that HFD-induced inflammatory metabolic disorders were alleviated by treatment with GPETAFLR. In conclusion, dietary lupine consumption can repair HFD-induced hepatic damage possibly via modifications of liver's lipid signalling pathways.