Proanthocyanidins: Impact on Gut Microbiota and Intestinal Action Mechanisms in the Prevention and Treatment of Metabolic Syndrome.

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.

Coagulation, Thrombogenesis, and Insulin Resistance Markers in Increased-Cardiovascular-Risk Subjects Consuming Improved-Fat Meat Products.

OBJECTIVES: Cardiovascular disease (CVD) risk is prevalent in high-meat-product consumers. The effect of consuming lipid-improved pâtés/frankfurters on plasma low-density lipoprotein (LDL)-cholesterol, thromboxane A2 (as TXB2), prostacyclin I2 (as 6-keto-PGF1α), activated partial thromboplastin time, fibrinogen, antithrombin, and insulin-resistance/sensitivity markers in volunteers at high CVD risk was studied. SUBJECTS/METHODS: Eighteen male volunteers enrolled in a blind crossover-controlled study consumed improved products during three 4-week periods: reduced fat (RF), n-3-enriched-RF (n-3RF), and normal fat (NF), separated by 4-week washouts. RESULTS: Fibrinogen and 6-keto-PG1α decreased (p < 0.05) following the RF period; LDL-cholesterol, TXB2, and 6-keto-PGF1α decreased (p < 0.05) after the n-3RF-period, while LDL-cholesterol, fibrinogen, TXB2, insulin, and Homostatic Model Assessment-insulin resistance (HOMA-IR) increased (at least p < 0.05) and QUICKI (Quantitative Insulin Sensitivity Check Index) decreased (p < 0.05) during the NF period. The rates of changes of fibrinogen, TXB2, 6-keto-PGF1α, and HOMA-IR differ between groups (repeated-measures test p < 0.05). Fibrinogen, insulin, and HOMA-IR differed significantly (p < 0.05) between RF and n-3RF period versus NF period, while that of TXB2 and 6-keto-PGF1α differed between n-3RF and NF periods (p < 0.05). CONCLUSIONS: The consumption of n-3RF meat products, followed by RF ones, partially reduced thrombogenesis, coagulation, and insulin-resistance markers. Thus, the inclusion of lipid-improved pâtés/frankfurters might be recommended into dietary strategies in at-CVD-risk volunteers.

The triglyceride-glucose index, an insulin resistance marker in newborns?

The study aims to assess the utility of the triglyceride-glucose index (TyG) as a marker of insulin resistance (IR) in neonates. TyG and the homeostatic model assessment (HOMA-IR) values were compared in 196 singleton, term normoweight and without distress newborns. A Decision Tree procedure (CHAID) was used to classify cases into groups or predict values of a dependent (Ln HOMA-IR) variable. Three nodes were drawn for TyG: ≤ 6.7, > 6.7-7.8 and > 7.8 (p < 0.0001; F = 20.52). The predictability of those TyG values vs HOMA-IR was statistically significant (p < 0.0001). It was neither affected by gender (p = 0.084), glucose challenge test (p = 0.138) classifications nor by the TyG node* glucose challenge test and TyG node*gender interactions (p = 0.456 and p = 0.209, respectively). Glucose, HOMA-IR, and the triglyceride/HDL cholesterol ratio increased progressively from node 1 to 3 for TyG while QUICKI decreased. CONCLUSION: In conclusion, TyG appears to be a suitable tool for identifying IR at birth, justifying the further insulin determination in those neonates. TyG ≥ 7.8 is recommended as cut-off point in neonates. The need for a follow-up study to confirm the TyG as early IR marker is desirable. WHAT IS KNOWN: • HOMA-IR and the triglyceride-glucose index (TyG) show a high correlation. • The TyG has been used as an insulin resistance marker in adults. WHAT IS NEW: • This is the first study where TyG has been assessed in neonates. • TyG appears to be a suitable and cheap tool for identifying insulin resistance at birth.

Silicon Alleviates Nonalcoholic Steatohepatitis by Reducing Apoptosis in Aged Wistar Rats Fed a High-Saturated Fat, High-Cholesterol Diet.

Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested.Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats.Methods: One-year-old male Wistar rats weighing ∼500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1) a high-saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO2/kg (control); 2) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO2/kg [high-cholesterol diet (Chol-C)]; and 3) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO2/kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining.Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P < 0.001). The score in Chol-Si rats (5.4) was intermediate and different from that in both other groups (P < 0.05). Several liver apoptosis markers-including hepatocyte terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling, cytosolic cytochrome c, apoptosis-inducing factor, caspases 9 and 3, and the mitochondrial Bcl-2-associated X protein (BAX)-to-B-cell lymphoma 2 (BCL2) ratio-were 9-45% lower in Chol-Si than in Chol-C rats (P < 0.05) and did not differ from values in the control group.Conclusions: Supplemental silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH.

Bioaccessibility of hydroxytyrosol and n-3 fatty acids as affected by the delivery system: simple, double and gelled double emulsions.

This study examines the influence of different food-grade n-3 PUFA-enriched simple emulsion (SE), double emulsion (DE) and gelled double emulsion (GDE) delivery systems on the extent of lipolysis, antioxidant capacity and the bioaccessibility of hydroxytyrosol (HTy). GDE emulsion offered better protection for HTy (89%) than the other systems (79% in SE and DE). The reducing capacity of the emulsions containing HTy were not altered during oral digestion. However, "in vitro" gastric and intestinal phases significantly reduced the antioxidant activity of all systems. The structural and physical state of GDE entailed a slowing-down of triacylglyceride hydrolysis (36.4%) in comparison with that of SE and DE (22.7 and 24.8% for SE and DE, respectively).

Silicon-Enriched Restructured Pork Affects the Lipoprotein Profile, VLDL Oxidation, and LDL Receptor Gene Expression in Aged Rats Fed an Atherogenic Diet.

BACKGROUND: Research has shown that silicon can play an important role in protecting against degenerative diseases. Restructuring pork by partially disassembling meat permits the incorporation of active components with potential functional effects. However, there has been no research to date on the impact that silicon, as a functional ingredient in restructured pork (RP), has on lipoprotein composition, metabolism, and oxidation. OBJECTIVE: This study was designed to evaluate the effect of silicon-enriched RP on lipemia, lipoprotein profile, and oxidation markers of aged rats fed high-fat, high-energy, cholesterol-enriched diets. METHODS: RP samples similar to commercial sausages (16% protein and 22% fat, wt:wt) were prepared by mixing lean pork and lard alone or with silicon (1.3 g Si/kg fresh matter) under controlled conditions and then freeze-dried. Saturated fat-rich diets were designed by mixing 78.3% purified diet with 21.7% freeze-dried RP. Three groups composed of 8 aged male Wistar rats (1 y old) were fed for 8 wk a control RP (C) diet, a cholesterol-enriched RP (Chol-C) diet [C diet enriched with 1.26% cholesterol plus 0.25% cholic acid, or a cholesterol and silicon-enriched RP (Chol-Si) diet (same as the Chol-C diet but containing silicon)]. Plasma lipid concentrations, lipoprotein profile, the degree of VLDL oxidation, and LDL receptor gene (Ldlr) expression were tested. RESULTS: Compared with the C diet, the Chol-C diet did not modify food intake or body weight but significantly increased (P < 0.05) plasma cholesterol (32%) and total lipids (19%), VLDL and intermediate density lipoprotein + LDL cholesterol (both >600%), total lipids and proteins (both >300%), and the degree of VLDL oxidation [conjugated dienes >250%; thiobarbituric acid-reactive substance (TBARS), 900%] and reduced Ldlr expression (64%) and liver arylesterase activity (54%). The Chol-Si diet partially normalized changes induced by the Chol-C diet. Compared with the Chol-C group, Chol-Si rats had lower VLDL compound concentrations (P < 0.001; e.g., 75% less VLDL cholesterol) and VLDL oxidation (65% less conjugated dienes and 85% less TBARS) but greater Ldlr expression (200%). CONCLUSIONS: Silicon added to RP strongly counterbalanced the negative effect of high-cholesterol-ingestion, functioning as an active hypocholesterolemic, hypolipemic, and antioxidative dietary ingredient in aged rats.

Adherence to Mediterranean diet during pregnancy and serum lipid, lipoprotein and homocysteine concentrations at birth.

BACKGROUND: Mediterranean diet consumption is associated to low prevalence of major degenerative diseases. Low Mediterranean-diet-adherence (MDA) score has been related to high insulin and homeostatic model assessment-insulin resistance levels at birth. The relationship between maternal MDA and offspring lipoprotein profile at birth has been scarcely reported. METHODS: Cross-sectional study aimed to study the relationship between pregnancy diet quality and serum lipid, arylesterase and homocysteine values at birth. Cord blood of the offspring of 35 women whose diets were classified as "adequate" or "inadequate" according to their 13-point MDA-score (≥7 or <7, respectively) were studied. RESULTS: MDA-scores did not significantly change through pregnancy. Low-MDA-score diets presented a higher atherogenic index, contained less fiber and folates, and had a lower (polyunsaturated + monounsaturated)/saturated fatty acids (PUFA + MUFA/SFA) ratio, more cholesterol, and higher SFA/carbohydrates (SFA/CHO) and ω-6/ω-3 PUFA ratios than their respective high-MDA-score counterparts. Mothers at the low MDA-score delivered neonates with high LDL-c (P = 0.049), Apo B (P = 0.040), homocysteine (P = 0.026) and Apo A1/Apo B ratio (P = 0.024). CONCLUSIONS: Neonates whose mothers consumed low MDA diets presented impaired lipoprotein and increased homocysteine levels at birth. A follow-up study on early cardiovascular disease prevention is needed to understand the importance of present findings later in life.

Effects of improved fat content of frankfurters and pâtés on lipid and lipoprotein profile of volunteers at increased cardiovascular risk: a placebo-controlled study.

PURPOSE: To study the effect of modified frankfurters and pâtés: (a) reduced-fat products (RF) (15.3 and 15.2 % fat, respectively); (b) n-3-enriched reduced-fat products (n-3 RF) (15.1 and 15.5 % fat, respectively); and (c) normal-fat products (NF) (18 and 30.8 % fat, respectively) on lipids, lipoproteins, atherogenic ratios, oxidized LDL, and blood pressure of volunteers at high CVD risk. METHODS: Twenty-two volunteers were enrolled in a sequential study of 3 consecutive 4-week periods separated by 4-week washout periods. RESULTS: LDL-cholesterol (p < 0.01), oxidized LDL, LDL-cholesterol/HDL-cholesterol (both p < 0.05) were significantly affected by the overall intervention. Compared to baseline, LDL-cholesterol decreased significantly (p = 0.012) during the RF period; the LDL-cholesterol/HDL-cholesterol ratio (p = 0.08) and the diastolic blood pressure (p = 0.06) also decreased, although non-significantly, after RF consumption. LDL-cholesterol (p = 0.040) and oxidized LDL (p = 0.016) increased significantly after NF product consumption; systolic blood pressure did not show significant variations after this period. No significant differences, in absolute or relative changes, were observed between RF and n-3 RF consumption for any parameter tested. However, LDL-cholesterol, oxidized LDL, and the LDL-cholesterol/HDL-cholesterol ratio were lower (12, 15 and 10 %, respectively) after n-3 RF versus NF product consumption. Oxidized LDL was approximately 15 % lower after RF versus NF product consumption. CONCLUSIONS: The regular consumption of RF meat products, enriched in n-3 fatty acids or not, positively affects the lipoprotein profile of volunteers, decreasing LDL-cholesterol and oxidized LDL levels and, thus, future risk of cardiovascular accident. On comparison with the effects of NF product intake, the responses to n-3 RF and RF products differ, and while n-3 RF intake induces a reduction in LDL-cholesterol, oxidized LDL-cholesterol, and LDL-cholesterol/HDL-cholesterol ratio, the intake of RF products modifies only the oxidized LDL level.

Organic silicon protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide effects.

BACKGROUND: Hydrogen peroxide (H2O2) is a toxic agent that induces oxidative stress and cell death. Silicon (Si) is a biological element involved in limiting aluminium (Al) absorption with possible preventive effects in Alzheimer's disease. However, Si has not yet been associated with other neuroprotective mechanisms. METHODS: The present experiments evaluated in the SH-SY5Y human neuroblastoma cell line the possible role of different Si G5 (50-1000 ng/mL) concentrations in preventing cellular death induced by H2O2 (400 µM, 24 hours). RESULTS: Our findings showed that H2O2 promoted cell death in the human SH-SY5Y cell cultures and this could be prevented by Si treatment. The loss in cell viability mediated by H2O2 was due to an apoptotic and necrotic process. Apoptotic death was incurred by regulating caspase-8 activity in the extrinsic pathway. The apoptotic and necrotic cell death induced by H2O2 was almost totally reversed by Si (50-500 ng/mL), indicating that it down-regulates both processes in H2O2 treated cells. CONCLUSIONS: According to our data, Si is able to increase SH-SY5Y cell survival throughout partially blocking cellular damage related to oxidative stress through a mechanism that would affect H2O2/ROS elimination.

Silicon-enriched meat positively improves plasma lipidaemia and lipoproteinaemia, LDLr, and insulin capability and the signalling pathway induced by an atherogenic diet in late-stage type 2 diabetes mellitus rats.

The impact of silicon as a functional ingredient in restructured meat (RM) on lipoprotein composition, metabolism, and oxidation on type 2 diabetes mellitus (T2DM) markers has never been studied. This study aims to evaluate the effect of silicon-enriched-meat consumption on lipidaemia, lipoprotein profile and metabolism, plasma arylesterase, and TBARS and their relationships with glycaemia, insulinaemia, and insulin-signaling markers in late-stage-T2DM rats fed a high-saturated-fat-high-cholesterol (HSFHC) diet. Saturated-fat diets with or without added cholesterol were formulated by mixing a 70% purified diet with 30% freeze-dried RM with or without added silicon. Three groups of seven Wistar rats each were tested. The ED group received the control RM in the framework of a high-saturated-fat diet as early-stage T2DM control. The other two groups received streptozotocin-nicotinamide administration together with the HSFHC diet containing the control RM (LD) or silicon-enriched RM (LD-Si). Scores were created to define the diabetic trend and dyslipidaemia. The ED rats showed hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, and triglyceride-rich-VLDLs, suggesting they were in early-stage T2DM. LD rats presented hyperglycaemia, hypoinsulinaemia, and reduced HOMA-beta and insulin signaling markers typical of late-stage T2DM along with hypercholesterolaemia and high amounts of beta-VLDL, IDL, and LDL particles and low arylesterase activity. All these markers were significantly (p < 0.05) improved in LD-Si rats. The diabetic trend and diabetes dyslipidaemia scores showed a high and significant correlation (r = 0.595, p < 0.01). Silicon-enriched-meat consumption counterbalances the negative effects of HSFHC diets, functioning as an active hypolipemic, antioxidant, and antidiabetic dietary ingredient in a T2DM rat model, delaying the onset of late-stage diabetes.

Cord-blood lipoproteins, homocysteine, insulin sensitivity/resistance marker profile, and concurrence of dysglycaemia and dyslipaemia in full-term neonates of the Mérida Study.

Early alterations in glucose homeostasis increase the risk of developing insulin resistance and obesity later in life. The concurrence of altered lipids and insulin sensitivity/resistance markers at birth has been scarcely investigated. The study aimed to ascertain level ranges of homocysteine (tHcyt), arylesterase (AE), lipids/lipoproteins, and insulin resistance/sensitivity markers in full-term neonates and to determine the concurrence effect of dyslipaemia and dysglycaemia on those parameters at birth. Participants were 197 full-term, 2.5 to <4.0 kg, without foetal distress Spanish newborns from the Mérida Study. Parameter percentiles for males and females were stated. The effect of the concurrence high glucose/high triglycerides (high glucose/high TG) or high glucose/low cholesterol transported by HDL (HDL-c) on tHcyt, LDL-c, HDL-c, lipoprotein (a) (Lp(a)), oxidised LDL (oxLDL), AE, glucose, insulin sensitivity (QUICKI) and insulin resistance index (HOMA-IR) was studied. Females had higher total cholesterol (TC), HDL-c, Apo A1, Lp(a) and HDL-c/Apo A1, but lower relative transport of TC (%TC) by the very low lipoprotein fraction than males. No gender differences were found for glucose, HOMA-IR and QUICKI. Neonates at the 2.5- to 2.999-kg range display more adequate HOMA-IR and QUICKI levels that their >3.0 kg counterparts. The concurrence of high glucose/high TG or high glucose/low HDL-c increased TC/HDL-c and HOMA-IR, but decreased, oxLDL, oxLDL/LDL-c and QUICKI with respect to that of low glucose/low TG or glucose/high HDL-c. The concurrence glucose/TG has predictive value for low QUICKI, whilst that of glucose/HDL-c for low QUICKI and high HOMA-IR, suggesting the importance of routine TG, HDL-c and glucose screening at birth as it would identify candidates for insulin resistance.

Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients suffering from metabolic syndrome with hyperglycemia are associated to dietary TAC and fruit consumption.

Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS), whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (-30% Energy): the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates), which was characterized by an increase of the meal frequency (seven-times/day), low glycemic load, high antioxidant capacity (TAC) and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra) diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL) values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI), waist circumference, fat mass and triacilglyceride (TG) levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

Autophagy, a relevant process for metabolic health and type-2 diabetes.

Introduction: Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.

Introducción: La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas de autofagia funcional (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus de tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2.

[Vitamin D and polymorphisms of VDR and GC genes in the severity and mortality from COVID-19. A systematic review]. / Vitamina D y polimorfismos de los genes VDR y GC en la severidad y mortalidad por COVID-19. Una revisión sistemática.

Introduction: Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.

Introducción: Estudios previos han señalado una posible relación entre la deficiencia de la vitamina D y la severidad de la enfermedad promovida por el SARS-CoV-2, reduciendo las complicaciones respiratorias y cardiovasculares causadas por una respuesta exacerbada del sistema inmune. Esta vitamina ejerce múltiples funciones que dependen de la presencia y niveles de diferentes proteínas, como el receptor de la vitamina D (VDR) y la proteína de unión de la vitamina D (DBP), y de la existencia de polimorfismos de un solo nucleótido (SNP) de los genes que codifican a estas proteínas. El objetivo de esta revisión es evaluar si algunos SNP de VDR y GC son factores de riesgo de las formas más severas de la enfermedad COVID-19 y si condicionan la respuesta a la suplementación con vitamina D. Se realizó una búsqueda en PubMed, Google Scholar y Scielo, encontrándose que son escasos los genotipados en pacientes afectados por COVID-19, aunque algunos trabajos hallan una relación entre diferentes alelos y la severidad de la enfermedad. Destaca el polimorfismo ApaI del gen VDR, el cual alelo menor "a" aumenta el riesgo de mortalidad por COVID-19 (OR = 11,828, CI: 2.493-56.104, p = 0,002). La divergencia de resultados en la eficacia de la suplementación de vitamina D sugiere la necesidad de un mayor número de estudios. En conclusión, el estudio de polimorfismos VDR y GC resulta fundamental para tratar eficazmente la deficiencia de vitamina D y en particular en la protección frente a COVID-19. Se necesitan estudios bien diseñados para dilucidar si los niveles plasmáticos de vitamina D juegan un papel de casualidad o causalidad.

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late-Stage Type 2 Diabetes Mellitus?

SCOPE: Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved. METHODS AND RESULTS: Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8). CONCLUSIONS: These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.

Effects of hydroxytyrosol-enriched sunflower oil consumption on CVD risk factors.

Inclusion of biophenols in traditional foods transforms them into functional foods that may help to decrease CVD risk. The aim of the present study was to determine whether the consumption of hydroxytyrosol-enriched sunflower oil (HSO) improves certain CVD biomarker values. A total of twenty-two healthy volunteers participated in a cross-over study involving two 3-week periods, separated by a 2-week washout period, in which volunteers consumed 800-1275 µg/d [corrected] of either HSO (45-50 mg/d of hydroxytyrosol) or non-enriched (control) sunflower oil. Total cholesterol, LDL-cholesterol, HDL-cholesterol, arylesterase activity, oxidised LDL and soluble vascular cell adhesion molecule (sVCAM-1) levels were measured in the plasma obtained at the beginning and at the end of each treatment period. The HSO group displayed a significantly higher level (P < 0·01) of arylesterase activity and significantly lower levels of oxidised LDL and sVCAM-1 (both P < 0·05) than the control group. These results suggest that HSO may help prevent CVD.

Effects of Nori- and Wakame-enriched meats with or without supplementary cholesterol on arylesterase activity, lipaemia and lipoproteinaemia in growing Wistar rats.

Some seaweeds exert antioxidant and hypocholesterolaemic properties. The effects of diets including restructured meats (RM) containing Wakame (W) or Nori (N) algae on arylesterase (AE) activity and lipoprotein concentration and composition were tested. In the present study, six groups of ten male growing Wistar rats each were fed a mix of 85 % AIN-93M diet and 15 % freeze-dried RM for 35 d. The control group (C) consumed control RM, the W and N groups consumed RM with 5 % W and 5 % N, respectively. The cholesterol-enriched C (CC), W (CW) and N (CN) groups consumed their corresponding basal diets with supplementary cholesterol (2·43 %) and cholic acid (0·49 %). Cholesterol in the diet induced lower (P < 0·001) growth ratios. Both W and N diets significantly increased AE activity. VLDL-cholesterol values were lower in N rats than in W rats. AE activity increased (P < 0·001) in CC and CW rats but not in CN rats compared with their corresponding counterparts. AE was lower (P < 0·05) in the CN group than in the CC and CW groups. The CN diet partially blocked (P < 0·001) the hypercholesterolaemic induction observed in CC and CW diets and reduced TAG levels (at least P < 0·05) with respect to those of CC rats. Although dietary cholesterol supplementation increased total cholesterol, VLDL-cholesterol and (intermediate-density lipoprotein+LDL)-cholesterol (all P < 0·001) in all rats, the CN diet moderately improved the lipoprotein profile of hypercholesterolaemic rats. Changes in AE activity and plasma cholesterol in CN rats but not in CW rats suggest a possible relationship between the two parameters. It is concluded that inclusion of RM enriched with N may be used in hypercholesterolaemic diets to improve lipoprotein metabolism.

Effects of APOA5 S19W polymorphism on growth, insulin sensitivity and lipoproteins in normoweight neonates.

Apolipoprotein (Apo) A5 is a protein involved in the activation of lipoprotein lipase (LPL) and the metabolism of triglyceride (TG)-rich lipoproteins. LPL plays a major role in the metabolism of TG-rich lipoproteins, and placental LPL activity is known to correlate positively with foetal fat deposition and size. We examine the association between the common APOA5 S19W polymorphism and neonatal anthropometrical measurements, lipoprotein and hormone concentrations, and insulin sensitivity in 58 normal weight Caucasian newborns from the Mérida cohort. Neonates with the W allele displayed lower BMI (P < 0.001), ponderal index (P < 0.001), birth weight (P < 0.01), insulin levels (P < 0.05), the insulin/cortisol ratio (P < 0.05), HOMA-R (P < 0.05) and Apo B values (P < 0.01), but higher oxidised LDL (LDLox) values and a higher LDLox/low-density lipoprotein (LDL) ratio (both P < 0.05) than S-homozygous newborns. The APOA5 S19W polymorphism was associated with foetal growth as well as with glucose and lipoprotein metabolism in the neonates. Concurrence of the S19W polymorphism in neonates and their mothers did not affect neonatal lipid and lipoprotein concentrations but was associated with impaired foetal growth. Specifically, W allele carriers displayed a higher degree of LDL oxidation and lower body weight, plasma insulin values, insulin/cortisol ratio and Apo B concentrations than homozygotes for the common S allele. In conclusion, these findings suggest that the W allele carriers received a less optimal nutrition during gestation and that their lipoprotein antioxidant status was inferior to that of their homozygous S allele counterparts.

Diabesity negatively affects transferrin saturation and iron status. The DICARIVA study.

AIMS: The relationship between iron status, obesity and type 2 diabetes mellitus (T2DM) has scarcely been tested. This study hypothesizes that patients with obesity and T2DM have altered iron metabolism. METHODS: 537 T2DM patients were selected from the cross-sectional DICARIVA study excluding patients with high-sensitivity-C-reactive-protein (hs-CRP) ≥  10 mg/L. Three groups according to body mass index (BMI) and waist perimeter (WP) were analysed: a) BMI < 30 kg/m2, non-high WP (n = 105); b) BMI < 30 kg/m2, high WP (n = 202); and c) diabesity, BMI ≥  30 kg/m2, high WP (n = 230). Group differences on cardiometabolic and iron status markers were tested. RESULTS: Women had significantly lower iron, ferritin, and transferrin saturation (TSAT) but higher transferrin and total iron binding capacity than men. Triglycerides/HDL-c ratio, as insulin-resistance (IR) marker, was higher in men while hs-CRP in women. TSAT was inversely related to BMI and hs-CRP. The diabesity group showed the highest hs-CRP (p < 0.001) and IR (p < 0.001) with the lowest TSAT (p = 0.003). CONCLUSIONS: Low TSAT was highly prevalent in diabesity, mainly in women, suggesting that IR, inflammation, and abdominal adiposity alter iron transport and accumulation. The convenience of iron supplementation in diabesity patients with low TSAT should be urgently assessed, due the pro-oxidant effects of excess iron.

Carob fruit extract-enriched meat, as preventive and curative treatments, improves gut microbiota and colonic barrier integrity in a late-stage T2DM model.

Epidemiological and experimental studies have suggested that dietary fiber and proanthocyanidins play an important role on gut microbiota (GM), colonic integrity and body health. Type 2 Diabetes Mellitus (T2DM) is a prevalent disease in which the modifications in the GM and colonic markers stand out. This manuscript hypothesizes the consumption of functional meat enriched in carob fruit extract [CFE; CFE-restructured meat (RM)] ameliorates the dysbiosis and colonic barrier integrity loss in a late-stage T2DM rat model induced by the conjoint action of a high-saturated-fat/high-cholesterol diet (Chol-diet) and a low dose of streptozotocin (STZ) plus a nicotinamide (NAD) injection. Three groups of eight rats were used: (1) D group, a T2DM control group, fed the Chol-diet; (2) ED group, a T2DM preventive strategy group fed the CFE-Chol-diet since the beginning of the study; and (3) DE group, a T2DM curative treatment group, fed the CFE-Chol-diet once the diabetic state was confirmed. The study lasted 8 weeks. Amount and variety of GM, feces short-chain-fatty acids (SCFAs), colonic morphology [crypt depth and density, goblet cells, proliferating cell nuclear antigen (PCNA) and transferase dUTP nick end labelling (TUNEL) indexes] and tight junctions were evaluated. A global colonic index combining 17 markers (GCindex) was calculated. ED rats displayed higher levels of GM richness, SCFAs production, crypt depth, and goblet cells than the D group. DE group showed lower Enterobacteriaceae abundance and greater TUNEL index and occludin expression in the distal colon than D counterpart. GCindex differentiated the colonic health status of the experimental groups in the order (ED > DE > D; P < 0.001) as a 17-51 range-quotation, ED, DE, and D groups displayed the values 43, 32.5, and 27, respectively. Thus, CFE-RM used as a T2DM preventive therapy could induce higher GM richness, more adequate SCFAs production, and better colonic barrier integrity. Furthermore, CFE-RM used with curative purposes induced more modest changes and mainly at the distal colonic mucosa. Further studies are needed to confirm this study's results, to ascertain the benefits of consuming proanthocyanidins-rich fiber during different T2DM stages.