Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

<p>Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.</p> <p>Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.</p> <p>Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.</p&gt

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers

Association between anthropometric markers of adiposity, adipokines and vitamin D levels.

Inverse association between serum levels of vitamin D and obesity has been pointed out in several studies. Our aim was to identify to the associations between vitamin D levels and a large panel of anthropometric markers and adipokines. Cross-sectional study including 6485 participants. Anthropometric markers included body mass index (BMI), % body fat, waist, waist-to-hip (WHR), waist-to-height (WHtR), conicity index, body roundness index (BRI) and a body shape index (ABSI). 55.7% of women and 60.1% of men presented with vitamin D deficiency. Vitamin D levels were negatively associated with most anthropometric markers, with correlation coefficients ranging between -0.017 (ABSI) and -0.192 (BMI) in women and between -0.026 (weight) and -0.130 (% body fat) in men. Vitamin D levels were inversely associated with leptin levels in both sexes and positively associated with adiponectin levels in women only. The likelihood of vitamin D deficiency increased with increasing adiposity levels, except for ABSI (women) and BMI (men). Total body fat, rather than localized or unevenly distributed body fat, is the adiposity marker most associated with decreased vitamin D levels. Monitoring vitamin D levels in people with overweight/obesity is essential

High Prevalence of Hypovitaminosis D in Adolescents Attending a Reference Centre for the Treatment of Obesity in Switzerland.

Hypovitaminosis D is common in populations with obesity. This study aimed at assessing (1) the prevalence of hypovitaminosis D and (2) the associations between vitamin D levels and cardiovascular risk factors in adolescents attending a reference centre for the treatment of obesity. Cross-sectional pilot study conducted in the paediatric obesity unit of the Lausanne university hospital, Switzerland. Participants were considered eligible if they (1) were aged between 10 to 16.9 years and (2) consulted between 2017 and 2021. Participants were excluded if (1) they lacked vitamin D measurements or (2) the vitamin D measurement was performed one month after the base anthropometric assessment. Hypovitaminosis D was considered if the vitamin D level was <30 ng/mL (<75 nmol/L). Severe obesity was defined as a BMI z-score > 3 SD. We included 52 adolescents (31% girls, mean age 13 ± 2 years, 33% with severe obesity). The prevalence of hypovitaminosis D was 87.5% in girls and 88.9% in boys. The vitamin D levels were inversely associated with BMI, Spearman r and 95% CI: -0.286 (-0.555; -0.017), p = 0.037; they were not associated with the BMI z-score: -0.052 (-0.327; 0.224), p = 0.713. The vitamin D levels were negatively associated with the parathormone levels (-0.353 (-0.667; -0.039), p = 0.028) and positively associated with the calcium levels (0.385 (0.061; 0.708), p = 0.020), while no association was found between vitamin D levels and blood pressure and lipid or glucose levels. almost 9 out of 10 adolescents with obesity in our cohort presented with hypovitaminosis D. Hypovitaminosis D does not seem to be associated with a higher cardiovascular risk profile in this group

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study.

Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D <sub>3</sub> (25(OH)D <sub>3</sub> ) with LC-MS/MS and explored associations using multiple logistic regression. The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m <sup>2</sup> with median C-Reactive Protein 1 mg/l. In logistic regressions, log <sub>2</sub> (Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D <sub>3</sub> with anti-SARS-CoV-2 IgG or IgA seropositivity. Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. CORONA IMMUNITAS:: ISRCTN18181860

1H NMR-Based Protocol for the Detection of Adulterations of Refined Olive Oil with Refined Hazelnut Oil

A (1)H NMR analytical protocol for the detection of refined hazelnut oils in admixtures with refined olive oils is reported according to ISO format. The main purpose of this research activity is to suggest a novel analytical methodology easily usable by operators with a basic knowledge of NMR spectroscopy. The protocol, developed on 92 oil samples of different origins within the European MEDEO project, is based on (1)H NMR measurements combined with a suitable statistical analysis. It was developed using a 600 MHz instrument and was tested by two independent laboratories on 600 MHz spectrometers, allowing detection down to 10% adulteration of olive oils with refined hazelnut oils. Finally, the potential and limitations of the protocol applied on spectrometers operating at different magnetic fields, that is, at the proton frequencies of 500 and 400 MHz, were investigated

Plasma monomeric ApoA1 and high-density lipoprotein bound ApoA1 are markedly decreased and associated with low levels of lipophilic antioxidants in sickle cell disease: A potential new pathway for therapy.

Patients with sickle cell disease (SCD) exhibit high levels of reactive oxygen species and low plasma levels of lipophilic antioxidants, which may contribute to end-organ damage and disease sequelae. Apolipoprotein A1, the major apolipoprotein of high-density lipoprotein (HDL), is mainly secreted by the intestine and liver in the form of monomeric ApoA1 (mApoA1) present in plasma. Cholesterol and α-tocopherol are delivered to ApoA1 via the ATP-binding cassette transporter, subfamily A, member 1 (ABCA1). We measured cholesterol, mApoA1, ApoA1, and lipophilic antioxidants in the plasma of 17 patients with SCD and 40 healthy volunteers. Mean HDL cholesterol (-C) levels in SCD patients and healthy subjects were 59.3 and 48.1 mg/dL, respectively, and plasma lutein, zeaxanthin, and α-tocopherol were 64.0%, 68.7%, and 9.1% lower, respectively. To compare SCD to healthy subjects with similar HDL-C, we also performed subgroup analyses of healthy subjects with HDL-C above or below the mean. In SCD, the mApoA1 level was 30.4 μg/mL; 80% lower than 141 μg/mL measured in healthy volunteers with similar HDL-C (56.7 mg/dL). The mApoA1 level was also 38.4% greater in the higher versus lower HDL-C subgroups (p = .002). In the higher HDL-C subgroup, lutein and zeaxanthin transported by HDL were 48.9% (p = .01) and 41.9% (p = .02) higher, respectively, whereas α-tocopherol was 31.7% higher (p = .003), compared to the lower HDL-C subgroup. Plasma mApoA1 may be a marker of the capacity of HDL to capture and deliver liposoluble antioxidants, and treatments which raise HDL may benefit patients with high oxidative stress as exemplified by SCD

LLL 44-4 : Micronutrients in acute disease and critical illness.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed

LLL 44 - 2 - Micronutrients in clinical nutrition: Vitamins.

Vitamins are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). Despite the small amounts that are required, the vitamins are essential both for maintenance of health, growth, and treatment of disease. After reminding about the principal function of all the vitamins, their needs and the clinical consequences of their deficit, the text present some common clinical problems: the impact of inflammation on the assessment of status. The reasons and diseases which cause increased requirements are presented, with the indications to monitoring of blood levels which remain the classical way to assess status in clinical settings. The text summarises the most relevant clinical manifestations of vitamins depletion and deficiency, the difficulties in assessing status, and makes recommendations for provision for medical nutrition therapy

LLL 44 - Module 3: Micronutrients in Chronic disease.

Micronutrients (MN), i.e. trace elements and vitamins, are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). The probability of MN depletion or deficiencies should be considered in all chronic illnesses, especially in those that can interfere with intake, digestion, or intestinal absorption. Low socio-economic status and food deprivation are recognized as the most prevalent reasons for MN deficiencies world-wide. Elderly multimorbid patients with multimodal therapy, as well as patients with long-lasting menu restrictions, are at high risk for both disease related malnutrition as well as multiple MN deficiencies, needing careful specific follow-up. The importance of monitoring MN blood levels along with CRP is essential for optimal care. Drug interactions are also highlighted. In patients with chronic conditions depending on medical nutrition therapy, the provision of adequate dietary reference intakes (DRI) of MN doses and monitoring of their adequacy belongs to standard of care