Glycomacropeptide as an Efficient Agent to Fight Pathophysiological Mechanisms of Metabolic Syndrome

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota

Association between siesta (daytime sleep), dietary patterns and the presence of metabolic syndrome in elderly living in Mediterranean area (MEDIS study):The moderating effect of gender

Objectives: Several lifestyle parameters including diet, physical activity and sleep were associated in isolation with the presence of Metabolic Syndrome (MetS) in adults, to date there is a paucity of studies which evaluated their combined role aging populations and especially with respect to gender. Therefore, the aim of the present study was to provide a global consideration of the lifestyle factors associated with MetS among elderly individuals. Design: Cross-sectional observational study. Setting: 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece. Participants: during 2005-2015, 2749 older (aged 65-100 years) from were voluntarily enrolled in the study. Measurements: Dietary habits, energy intake, physical activity status, sociodemographic characteristics, lifestyle parameters (sleeping and smoking habits) and clinical profile aspects were derived through standard procedures. The presence of MetS was defined using the definition provided by NCEP ATP III (revised) and cluster analysis was used to identify overall dietary habit patterns. Results: The overall prevalence of MetS in the study sample was 36.2%, but occurred more frequently in females (40.0% vs. 31.8%, respectively, p=0.03). Individuals with MetS were more likely to sleep during the day (89.4% vs. 76.8% respectively, p=0.039) and frequent ‘siesta’ was positively linked to the odds of MetS presence in females (Odds Ratio (OR) =3.43, 95% Confidence Intervals (CI): 1.08-10.9), but not for men (p=0.999). The lower carbohydrate (i.e., 45.2% of total daily energy, 120±16gr/day) dietary cluster was inversely associated with the odds for MetS presence, but only for men (OR=0.094, 95%CI: 0.010-0.883). Conclusions: Lifestyle parameters including sleep and diet quality are strongly associated with the presence of MetS in elderly cohort, but different their level of influence appears to be different, depending on gender. Further research is needed to better consider the role of lifestyle characteristics in the management of MetS in clinical practice

Plasma fatty acid composition in French-Canadian children with non-alcoholic fatty liver disease: Effect of n-3 PUFA supplementation

International audienceNon-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of liver disease worldwide. As the NAFLD pathogenesis is associated with diet and lifestyle, the aims of the present work are to assess fatty acid (FA) composition in NAFLD young French-Canadian, to determine whether treatment with n-3 FA improves the plasma FA profile, and to define the time on the effectiveness of n-3 FA supplementation. Baseline characteristics of the NAFLD subjects show increased, anthropometric and biochemical parameters. Their plasma FA composition is characterized by a percent increase in total n-6 FA and a high proportion of saturated and total monounsaturated FA, as well as a decrease in Delta5 and increase in Delta6 desaturases. In conclusion, our results document for the first time the composition of plasma FAs in NAFLD young French Canadian and the efficacy of 3-month supplementation to improve the proportion of n-3 FA in their plasma

Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease

International audienceChylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR-Cas9 system. We found that deletion or mutation of Sar1b in mice resulted in late-gestation lethality of homozygous embryos. Moreover, compared with WT mice, heterozygotes carrying a single disrupted Sar1b allele displayed lower plasma levels of triglycerides, total cholesterol, and HDL-cholesterol, along with reduced CM secretion following gastric lipid gavage. Similarly, decreased expression of apolipoprotein B and microsomal triglyceride transfer protein was observed in correlation with the accumulation of mucosal lipids. Inefficient fat absorption in heterozygotes was confirmed via an increase in fecal lipid excretion. Furthermore, genetically modified Sar1b affected intestinal lipid homeostasis as demonstrated by enhanced fatty acid β-oxidation and diminished lipogenesis through the modulation of transcription factors. This is the first reported mammalian animal model with human Sar1b genetic defects, which reproduces some of the characteristic CRD features and provides a direct cause-effect demonstration

Non-alcoholic fatty liver disease severity and metabolic complications in obese children: impact of omega-3 fatty acids

Although n-3 polyunsaturated fatty acids (PUFA) revealed promising therapeutic results in non-alcoholic fatty liver disease (NAFLD), which is considered as the most prevalent cause of chronic hepatic disease, inconsistencies are calling for further confirmatory trials to demonstrate therapeutic efficacy and safety. The study, registered as NCT02201160 on www.clinicaltrials.gov, was designed to compare two groups of NAFLD with a different severity, and to evaluate the efficacy of n-3 PUFA supplementation. Twenty young male participants of French Canadian origin with NAFLD were enrolled and classified into moderate (mNAFLD) and severe (sNAFLD) fatty liver groups, according to transaminase levels, ultrasonography, NAFLD Activity Score and Fatty Liver Index (FLI). The sNAFLD patients were assigned to consume 2 g of n-3 PUFA for 6 months. sNAFLD patients displayed higher insulinemia, insulin resistance (IR), oxidative stress (OxS), systolic blood pressure and the risk lipid indicators of cardiovascular diseases. Supplementation of n-3 PUFA for 6 months resulted in a significant increase in concentrations of eicosapentaenoic and docosahexaenoic acids in red blood cells along with an attenuation of hepatic steatosis as reflected by the reduction of the FLI, ALT and ALT/AST ratio. Moreover, the n-3 PUFA improved the lipid profile and carotid intima-media thickness, while reducing metabolic and OxS markers as well as raising adiponectin. In conclusion, NAFLD severity was essentially related to IR. Treatment with n-3 PUFA has an evidently beneficial effect on liver steatosis and related metabolic abnormalities. Furthermore, the cross association of omega-3 index with cardiometabolic markers may serve as a predictor for cardiovascular risk disorders in NAFLD. (C) 2018 Elsevier Inc. All rights reserved

Antioxidant Status and DNA Damage in Children with Attention Deficit Hyperactivity Disorder with or without Comorbid Disruptive Behavioral Disorders

Objective: The aim of this study is to investigate oxidative stress and DNA damage among children with attention deficit hyperactivity disorder (ADHD) with or without disruptive behavioral disorders (DBD). Methods: A total of 49 treatment naive children (M/F: 40/9) who were diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria were included. The patients with ADHD were divided into two groups, those with ADHD alone (n= 25) and ADHD plus DBD (n= 24). The control group consisted of 40 age-and sex-similar healthy children. The Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Life-time version (K-SADS-PL) was applied to all children. Children's teachers completed the Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S). Serum glutathione peroxidase (GPx), coenzyme Q, 8-hydroxy-2-deoxyguanosine (8-OHdG) and superoxide dismutase (SOD) levels were measured by the ELISA method using commercial kits. Results: There were no significant differences in serum GPx, SOD, CoQ and 8-OHdG levels among the pure ADHD, ADHD plus DBD and the control groups (p>0.05). No statistically significant correlations were found between the severity of ADHD symptoms and GPx, SOD, CoQ and 8-OHdG levels. Conclusion: Our study suggests that oxidative stress may not play a key role in the pathogenesis of pure ADHD and ADHD plus DBD.Dicle University Scientific Research Coordination Body [12-TF-124]We would like to thank our patients and their parents for taking part in this study. This study received financial support from Dicle University Scientific Research Coordination Body with project number of 12-TF-124

Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder

Attention deficit/hyperactivity disorder (ADHD) is one of the most common child psychiatric disorders, and is often treated with stimulant medication. Nonpharmacological treatments include dietary supplementation with omega-3 fatty acids, although their effectiveness remains to be shown conclusively. In this study, we investigated the effects of dietary omega-3 fatty acid supplementation on ADHD symptoms and cognitive control in young boys with and without ADHD. A total of 40 boys with ADHD, aged 8–14 years, and 39 matched, typically developing controls participated in a 16-week double-blind randomized placebo-controlled trial. Participants consumed 10 g of margarine daily, enriched with either 650 mg of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) each or placebo. Baseline and follow-up assessments addressed ADHD symptoms, fMRI of cognitive control, urine homovanillic acid, and cheek cell phospholipid sampling. EPA/DHA supplementation improved parent-rated attention in both children with ADHD and typically developing children. Phospholipid DHA level at follow-up was higher for children receiving EPA/DHA supplements than placebo. There was no effect of EPA/DHA supplementation on cognitive control or on fMRI measures of brain activity. This study shows that dietary supplementation with omega-3 fatty acids reduces symptoms of ADHD, both for individuals with ADHD and typically developing children. This effect does not appear to be mediated by cognitive control systems in the brain, as no effect of supplementation was found here. Nonetheless, this study offers support that omega-3 supplementation may be an effective augmentation for pharmacological treatments of ADHD (NCT01554462: The Effects of EPA/DHA Supplementation on Cognitive Control in Children with ADHD; http://clinicaltrials.gov/show/NCT01554462).Neuropsychopharmacology advance online publication, 22 April 2015; doi:10.1038/npp.2015.73