Lipids and lipid signaling molecules in human milk and infant formula, a chemical characterization of relevant biochemical components.

Breastfeeding is the gold standard in infant nutrition and continuous researches aim to optimize infant formula composition as the best alternative available. Human milk lipid content provides more than 50% of energy requirements for infants together with essential vitamins, polyunsaturated fatty acids, and other bioactive components. While fatty acids and vitamins human milk content has been extensively studied and, when needed those have been added to infant formulas, less is known about polyunsaturated fatty acids functional derivatives and other bioactive components. Here we describe the comparison of lipid compositions in breast milk from 22 healthy volunteers breastfeeding mothers and the six most common infant formula devoting particular attention to two families of signaling lipids, endocannabinoids, and eicosanoids. The main differences between breast milk and formulas lie in a variety of saturated fatty and unsaturated fatty acids, in the total amount (45-95% less in infant formula) and a variety of endocannabinoids and eicosanoids (2-AG, 5(s)HETE, 15(S)-HETE and 14,15-EET).

Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review.

BACKGROUND: Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023. METHODS: The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus. RESULTS: Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects. CONCLUSIONS: Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.

Ultrastructural features mirror metabolic derangement in human endothelial cells exposed to high glucose.

High glucose-induced endothelial dysfunction is the early event that initiates diabetes-induced vascular disease. Here we employed Cryo Soft X-ray Tomography to obtain three-dimensional maps of high D-glucose-treated endothelial cells and their controls at nanometric spatial resolution. We then correlated ultrastructural differences with metabolic rewiring. While the total mitochondrial mass does not change, high D-glucose promotes mitochondrial fragmentation, as confirmed by the modulation of fission-fusion markers, and dysfunction, as demonstrated by the drop of membrane potential, the decreased oxygen consumption and the increased production of reactive oxygen species. The 3D ultrastructural analysis also indicates the accumulation of lipid droplets in cells cultured in high D-glucose. Indeed, because of the decrease of fatty acid ß-oxidation induced by high D-glucose concentration, triglycerides are esterified into fatty acids and then stored into lipid droplets. We propose that the increase of lipid droplets represents an adaptive mechanism to cope with the overload of glucose and associated oxidative stress and metabolic dysregulation.

A Randomized Double-Blind Placebo-Controlled Clinical Study to Evaluate the Effect on the Weight of a Medical Device with Polyglucosamine L112 in a Group of Overweight and Obese Subjects.

BACKGROUND: Overweight and obesity have reached epidemic proportions and safe treatments are needed to heal these diseases. OBJECTIVE: The objective of this study is to examine the activity of a medical device based on polyglucosamine polymers (PG) on body weight (BW) reduction, insulin resistance, and the serum levels of fat-soluble vitamins and glucosamine. METHODS: A double-blind placebo-controlled interventional study comparing PG and a placebo (PL) was conducted. One hundred and fifty overweight or obese cases were treated, divided into two groups for a period of 90 days at the dosage of 3 g/day. RESULTS: One hundred and nineteen cases (58 with PG and 61 with PL, respectively) concluded the treatment. PG was more effective than the PL on the reduction of BW and insulin resistance. No modification of fat-soluble vitamins (Vit A, E, D3, K1) and glucosamine levels was shown. Total cholesterol levels were significantly more reduced in the PG group compared to the PL group as it was for subjects with a BW decrease of >5%. CONCLUSIONS: PG acts as a safe medical device, is not absorbed, and binds lipids in the upper gastrointestinal tract, reducing their availability, with a significant activity on the reduction of BW, insulin resistance, and cholesterol levels without the modification of fat-soluble vitamins.

Determination of the quality of lipoproteins by Raman spectroscopy in obese and healthy subjects.

Lipoproteins (LPs) are multimolecular complexes of lipids and proteins responsible for transporting fatty acids, cholesterol, and micronutrients (carotenoids) through the body. The quantification of triglycerides and cholesterol carried by lipoproteins is a leading clinical parameter to assess the increased risk of cardiovascular events. However, in recent times, the study of the overall "quality" of lipoproteins, defined by their biochemical composition and oxidation state, has emerged as necessary to improve the definition of the cardiovascular risk. In this work, we present Raman spectroscopy (RS) as an effective method to immediately detect the functional groups relative to the principal biochemical components and the level of unsaturated lipids present in LPs. Furthermore, we show how RS can reveal the differences in the biochemical composition and oxidation state of LPs extracted from a cohort of obese patients (Ob) and a control group of healthy subjects (HC). In particular, RS revealed how low-density lipoproteins (LDLs) from obese patients are enriched in triglycerides and more oxidized than those from the control group, while high-density lipoproteins (HDLs) from Ob patients were depleted in cholesterol and phospholipids. RS analysis also allowed the study of the relationship between the levels of carotenoids present in the different classes of LPs highlighting how this parameter depends on the disease severity. Overall, these results demonstrated that RS is a viable approach for quickly and effectively gaining information on LPs' biochemical composition and oxidation state, providing an immediate measure of their quality. Besides, RS further proved the role of LPs in obesity and metabolic dysfunctions.

Associations between Maternal Dietary Patterns, Biomarkers and Delivery Outcomes in Healthy Singleton Pregnancies: Multicenter Italian GIFt Study.

Background: Maternal nutrition represents a critical risk factor for adverse health outcomes in both mother and offspring. We aimed to investigate associations between maternal nutritional habits, biomarker status, and pregnancy outcome among Italian healthy normal-weight pregnancies. Methods: Multicenter prospective cohort study recruiting Italian healthy normal-weight women with singleton spontaneous pregnancies at 20 ± 2 weeks (T1) in Milan and Naples. All patients underwent nutritional evaluations by our collecting a 7-day weighed dietary record at 25 ± 1 weeks (T2) and a Food Frequency Questionnaire at 29 ± 2 weeks (T3). Maternal venous blood samples were collected at T3 to assess nutritional, inflammatory and oxidative biomarker concentrations (RBCs folate, vitamin D, hepcidin, total antioxidant capacity). Pregnancy outcomes were collected at delivery (T4). General linear models adjusted for confounding factors were estimated to investigate associations between maternal dietary pattern adherence, nutrient intakes, biomarker concentrations and delivery outcomes. Results: 219 healthy normal-weight pregnant women were enrolled. Vitamin D and RBCs folate concentrations, as well as micronutrient intakes, were consistently below the recommended range. In a multi-adjusted model, maternal adherence to the most prevalent 'high meat, animal fats, grains' dietary pattern was positively associated with hepcidin concentrations and negatively associated with gestational age at delivery in pregnancies carrying female fetuses. Hepcidin plasma levels were further negatively associated to placental weight, whereas vitamin D concentrations were positively associated to neonatal weight. Conclusions: A high adherence to an unbalanced 'high meat, animal fats, grains' pattern was detected among Italian normal-weight low-risk pregnancies, further associated with maternal pro-inflammatory status and gestational age at delivery. This evidence underlines the need for a dedicated nutritional counseling even among low-risk pregnancies.

A Potential Interplay between HDLs and Adiponectin in Promoting Endothelial Dysfunction in Obesity.

Obesity is an epidemic public health problem that has progressively worsened in recent decades and is associated with low-grade chronic inflammation (LGCI) in metabolic tissues and an increased risk of several diseases. In particular, LGCI alters metabolism and increases cardiovascular risk by impairing endothelial function and altering the functions of adiponectin and high-density lipoproteins (HDLs). Adiponectin is an adipokine involved in regulating energy metabolism and body composition. Serum adiponectin levels are reduced in obese individuals and negatively correlate with chronic sub-clinical inflammatory markers. HDLs are a heterogeneous and complex class of lipoproteins that can be dysfunctional in obesity. Adiponectin and HDLs are strictly interdependent, and the maintenance of their interplay is essential for vascular function. Since such a complex network of interactions is still overlooked in clinical settings, this review aims to highlight the mechanisms involved in the impairment of the HDLs/adiponectin axis in obese patients to predict the risk of cardiovascular diseases and activate preventive countermeasures. Here, we provide a narrative review of the role of LGCI in altering HDLs, adiponectin and endothelial functions in obesity to encourage new studies about their synergic effects on cardiovascular health and disease.

Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca2+ and Voltage-Activated K+ Channel Activity in Human Insulin Secretion.

Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca2+ and voltage-activated K+ channel (BKC). The KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K+ current. The phenotype of this variant includes developmental delay, and visceral and connective tissue malformations. So far, only three cases of LWAS have been described, one of which also had neonatal diabetes (ND). We present the case of a newborn affected by LIWAS carrying the p.(Gly375Arg) variant who manifested diabetes in the first week of life. The description of our case strongly increases the frequency of ND in LIWAS patients and suggests a role of BK inactivation in human insulin secretion. The knowledge on the role of BKC in insulin secretion is very poor. Analyzing the possible mechanisms that could explain the association of LIWAS with ND, we speculate that BK inactivation might impair insulin secretion through the alteration of ion-dependent membrane activities and mitochondrial functions in ß-cells, as well as the impaired intra-islet vessel reactivity.

HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity.

High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the risk for cardiovascular disease, plasma HDL cholesterol levels do not predict the functionality and composition of HDLs. The importance of defining both the amount of cholesterol transported and lipoprotein functionality has recently been highlighted. Indeed, different clinical conditions such as obesity, diabetes mellitus type 2 (T2DM), and cardiovascular disease (CVD) can alter the HDL functionality, converting normal HDLs into dysfunctional ones, undergoing structural changes, and exhibiting proinflammatory, pro-oxidant, prothrombotic, and proapoptotic properties. The aim of the current review is to summarize the actual knowledge concerning the physical-chemical alteration of HDLs related to their functions, which have been found to be relevant in several pathological conditions associated with systemic inflammation and oxidative stress.

The Contribution of Dietary Magnesium in Farm Animals and Human Nutrition.

Magnesium (Mg) is a mineral that plays an essential role as cofactor of more than 300 enzymes. Mg in farm animals' and human nutrition is recommended to avoid Mg deficiency, ensure adequate growth and health maintenance. Mg supplementation above the estimated minimum requirements is the best practice to improve farm animals' performances (fertility and yield) and food products' quality, since the performance of farm animals has grown in recent decades. Mg supplementation in pigs increases meat quality and sows' fertility; in poultry, it helps to avoid deficiency-related health conditions and to improve meat quality and egg production by laying hens; in dairy cows, it serves to avoid grass tetany and milk fever, two conditions related to hypomagnesaemia, and to support their growth. Thus, Mg supplementation increases food products' quality and prevents Mg deficiency in farm animals, ensuring an adequate Mg content in animal-source food. These latter are excellent Mg sources in human diets. Sub-optimal Mg intake by humans has several implications in bone development, muscle function, and health maintenance. This review summarizes the main knowledge about Mg in farm animals and in human nutrition.

Magnesium in Obesity, Metabolic Syndrome, and Type 2 Diabetes.

Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.

Going to the roots of reduced magnesium dietary intake: A tradeoff between climate changes and sources.

Magnesium is essential in plants where it is associated with chlorophyll pigments and serves as a cofactor of enzymes implicated in photosynthesis and metabolism. It is an essential nutrient for animals, involved in hundreds metabolic reaction and crucial for the biological activity of ATP. Not surprisingly, magnesium deficiency is detrimental for the health of plants and animals. In humans, subclinical magnesium deficiency is common and generates chronic inflammation, which is the common denominator of a wide range of mental and physical health problems from metabolic diseases to cognitive impairment, from osteopenia and sarcopenia to depression. It is ascertained that magnesium content in fruits and vegetables dropped in the last fifty years, and about 80% of this metal is lost during food processing. As a consequence, a large percentage of people all over the world does not meet the minimum daily magnesium requirement. In this scoping review, we summarize how agronomic and environmental factors, including global warming, affect magnesium content and availability in the soil and, consequently, in the food chain, with the aim of attracting the interest of botanists, agronomists, animal and human nutritionists and physicians to work on a strategy that grants adequate magnesium intake for everybody.

Effect of Polyglucosamine on Weight Loss and Metabolic Parameters in Overweight and Obesity: A Systemic Review and Meta-Analysis.

The use of dietary supplements for weight loss has gained significant momentum. Polyglucosamine, a chitosan derivative, is a dietary supplement increasingly used for weight loss. In this meta-analysis, we systematically summarized and quantified the key findings of four randomized, placebo-controlled clinical trials examining the effects of polyglucosamine supplementation and caloric restriction, and physical activity on body weight, body mass index (BMI), and waist circumference in subjects with overweight and obesity. The control group was set with a physical activity from 6-7 MET-h/week activity and up to 21 MET-h/week activity with caloric restriction. Compliance in the latter trials was reported via a follow-up questionnaire with the individual participants. The analysis included 399 subjects followed for a period ranging from 12 weeks to one year. Subjects' age ranged from 21-75 years, BMI from 26-45 kg/m2, and all were white European or Caucasian in ethnicity. The meta-analyzed mean differences for random effects showed that polyglucosamine supplementation improves weight loss by -1.78 kg [-2.78, -0.79], BMI by -1.52 kg/m2 [-3.58, 0.54], and improves waist circumference reduction by -1.45 cm [-2.77, -0.12]. In conclusion, the use of polyglucosamine supplementation in conjunction with lifestyle behavioral therapies can be effective for weight reduction. Further studies are needed to examine the long-term effects of polyglucosamine supplementation on weight loss and other metabolic parameters.

Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study.

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.

A structural equation model to assess the pathways of body adiposity and inflammation status on dysmetabolic biomarkers via red cell distribution width and mean corpuscular volume: a cross-sectional study in overweight and obese subjects.

BACKGROUND: A study has been performed in overweight and obese subjects to assess the effects of adiposity and inflammation indicators on dysmetabolic biomarkers via red cell distribution width (RDW) and mean corpuscular volume (MCV), taking into account pro-antioxidant balance. METHODS: Data from 166 overweight subjects were analyzed by a path analysis model using structural equation modelling (SEM) to evaluate the direct and indirect pathway effects of adiposity, measured by body mass index (BMI) and waist circumference (WC), and inflammation status, measured by pro-antioxidant balance [reactive oxygen species (ROS)], lag-time and slope and C-reactive protein (CRP) values on dysmetabolic biomarkers, via RDW and MCV. RESULTS: BMI was strongly linked to CRP and ROS levels. Moreover, there was a significant negative decrease of MCV (1.546 femtoliters) linked to BMI indirectly via high CRP levels. Furthermore, WC affected RDW, indicating a possible mediatory role for RDW in relation to the relationship between WC and homeostatic model assessment (HOMA), insulin and high density lipoprotein (HDL), respectively. This was evident by the elevated HOMA and insulin levels and the decreased levels of HDL. Finally, ROS-related markers did not affect directly RDW and MCV. CONCLUSION: The reported outcomes suggest that RDW might play a mediatory role in the relationship between WC and the dysmetabolic outcomes in overweight and obese individuals. CRP seems to modulate the linkage between BMI and MCV. This study provides the backbone structure for future scenarios and lays the foundation for further research on the role of RDW and MCV as suitable biomarkers for the assessment of cardiovascular disease (HDL-cholesterol), inflammatory bowels and insulin resistance.

N-Oleoyl-Phosphatidyl-Ethanolamine and Epigallo Catechin-3-Gallate Mitigate Oxidative Stress in Overweight and Class I Obese People on a Low-Calorie Diet.

Oxidative stress and lipid peroxidation are considered key factors linking obesity with its associated complications. Epigallo catechin-3-gallate (EGCG) and oleoylethanolamide, together with its phospholipid precursor N-oleoyl-phosphatidylethanolamine (NOPE), are nutritional compounds that might improve the oxidative stress status of obese people. Unfortunately, the bioavailability of these compounds is low; however, the coadministration of NOPE with EGCG has been shown to ameliorate both the plasma availability of EGCG and the intestinal levels of NOPE in rats. This double-blind placebo-controlled study investigated the effects of 2 months' supplementation with EGCG complexed with NOPE, combined with moderate energy restriction, on plasma oxidative status of overweight and class I obese subjects. A total of 138 subjects (body mass index: 25-35 kg/m2) were recruited and randomized into two groups: the first (n = 67) received caps of placebo and the second (n = 71) caps of an oily dispersion of EGCG complexed with NOPE for 2 months. Subjects' supplementation was combined with moderate energy restriction (-800 kcal/day). Plasma oxidative status was determined by measuring the levels of oxidized low-density lipoprotein (Ox-LDL), malondialdehyde and reactive oxygen metabolites, and by calculating the lag time and the slope of Cu-induced lipid peroxidation kinetics. In total 116 subjects (27 M/89 F) completed the supplementation period, 49 in the placebo group and 67 in the treated group. Treatment induced a similar significant weight reduction in the two groups. Moreover, we found the mean changes of Ox-LDL significantly lower and the mean changes of antioxidant capacity (lag time) significantly higher in NOPE-EGCG group than in placebo group (treatment effect mean difference: -3.15 UL, P < .044 and +5.37 min, P < .0347, respectively). EGCG plasma levels were detectable only after 2 months of NOPE-EGCG diet. The NOPE-EGCG integration to a low-energy diet seems, therefore, useful for ameliorating oxidative stress-related markers, which are concomitant causes of obesity-induced disorders.

Reactive oxygen species are implicated in altering magnesium homeostasis in endothelial cells exposed to high glucose.

Transient Receptor Potential Melastatin (TRPM)7 is important in maintaining the intracellular homeostasis of magnesium (Mg), which is instrumental for vital cellular functions. Since the upregulation of TRPM7 has been proposed as a marker of endothelial dysfunction, we evaluated the effects of high glucose, which markedly impacts endothelial performance, on TRPM7 and intracellular Mg homeostasis in human macrovascular endothelial cells. We show that glucose-induced free radicals increase the amounts of TRPM7 as well as total intracellular magnesium. On the contrary, the highly selective Mg transporter MagT1 is not modulated by high glucose, hydrogen peroxide and low extracellular magnesium. We conclude that in endothelial cells high glucose alters Mg homeostasis through the upregulation of TRPM7.

Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells.

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0-20 µM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 µM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity.

Impaired fluidity and oxidizability of HDL hydrophobic core and amphipathic surface in dyslipidemic men.

OBJECTIVE: To examine and compare the composition, fluidity and oxidizability of HDL hydrophobic core and amphipathic surface of two groups of adult males (25kg/m²