Nathalie Nicod

Nestlé (Switzerland)

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Francesco Visioli

IMDEA Food

Elena Giordano

Rutgers, The State University of New Jersey

Alberto Dávalos

Instituto de Salud Carlos III

Robert S. Parker

University of Pittsburgh

Luc Tappy

University of Bern

Ramón Gomis

Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas

Christine Besse

University of Lausanne

Marta Pradas-Juni

Novo Nordisk Foundation

Stefan Ehling

Abbott (United States)

Virginia Maestro

Madrid Institute for Advanced Studies

Cooperative Institutions

Nestlé (Switzerland)

Madrid Institute for Advanced Studies

Instituto de Salud Carlos III

Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition

IMDEA Food

Universidad Autónoma de Madrid

Centro de Investigación Biomédica en Red

Consejo Superior de Investigaciones Científicas

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Hospital Clínic de Barcelona

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Changes in Insulin Secretion and Glucose Metabolism Induced by Dexamethasone in Lean and Obese Females

Obesity Research (2005)

Christine Besse Nathalie Nicod Luc Tappy

Abstract Objective : In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2‐day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short‐term dexamethasone administration in obese women. Research Methods and Procedures : Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low‐dose dexamethasone administration. A two‐step hyperglycemic clamp (7.5 and 10 mM glucose) with 6, 6 2 H 2 glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. Results : Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. Discussion : Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately.

Carbohydrate Metabolism

Glucose clamp technique

10.1038/oby.2005.41

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Citations (40)

Metabolic Adaptations to Dexamethasone‐Induced Insulin Resistance in Healthy Volunteers

Obesity Research (2003)

Nathalie Nicod Vittorio Giusti Christine Besse Luc Tappy

Abstract Objective : Insulin resistance is observed in individuals with normal glucose tolerance. This indicates that increased insulin secretion can compensate for insulin resistance and that additional defects are involved in impaired glucose tolerance or type 2 diabetes. The objective of this study was to evaluate a procedure aimed at assessing the compensatory mechanisms to insulin resistance. Research Methods and Procedures : Eight healthy nonobese female patients were studied on two occasions, before and after administration of 2 mg/d dexamethasone for 2 days during a two‐step hyperglycemic clamp. Insulin secretion was assessed from plasma insulin concentrations. Insulin sensitivity was assessed from the ratio of whole‐body glucose use (6, 6 2 H 2 glucose) to plasma insulin concentrations. This procedure is known to induce a reversible impairment of glucose tolerance and insulin resistance. Results : In all subjects, dexamethasone induced a decrease in insulin sensitivity and a proportionate increase in first‐phase insulin secretion and in insulin concentrations at both steps of glycemia. The resulting hyperinsulinemia allowed the restoration of normal whole‐body glucose uptake and the suppression of plasma free fatty acids and triglycerides. In contrast, the suppression of endogenous glucose production was impaired after dexamethasone ( p < 0.01). Discussion : Increased insulin secretion fully compensates dexamethasone‐induced insulin resistance in skeletal muscle and adipose tissue but not in the liver. This suggests that failure to overcome hepatic insulin resistance can impair glucose tolerance. The compensatory insulin secretion in response to insulin resistance can be assessed by means of a hyperglycemic clamp after a dexamethasone challenge.

Hyperinsulinemia

Glucose clamp technique

10.1038/oby.2003.90

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Citations (124)

Molecular Targets of Omega 3 and Conjugated Linoleic Fatty Acids – “Micromanaging” Cellular Response

Frontiers in Physiology (2012)

Francesco Visioli Elena Giordano Nathalie Nicod Alberto Dávalos

Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and conjugated linoleic acid, as paradigmatic molecules that can be exploited both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.

10.3389/fphys.2012.00042

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Vitamin E Secretion by Caco-2 Monolayers to APOA1, but Not to HDL, Is Vitamer Selective

Journal of Nutrition (2013)

Nathalie Nicod Robert S. Parker

Scavenger Receptor

10.3945/jn.113.176834

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Citations (26)

Docosahexaenoic Acid Modulates the Enterocyte Caco-2 Cell Expression of MicroRNAs Involved in Lipid Metabolism

Journal of Nutrition (2014)

Judit Gil-Zamorano Roberto Martín‐Hernández Lidia Daimiel Kris Richardson Elena Giordano

Dicer

Enterocyte

Ribonuclease III

10.3945/jn.113.189050

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Citations (73)

Role of the single nucleotide polymorphism rs7903146 of TCF7L2 in inducing nonsense-mediated decay

SpringerPlus (2014)

Nathalie Nicod Marta Pradas-Juni Ramón Gomis

The single nucleotide polymorphism (SNP) rs7903146 (C/T), located in intron 4 of the transcription factor 7-like 2 gene (TCF7L2), has been associated with an increased risk of developing Type 2 Diabetes, although the molecular mechanism remain elusive. The TCF7L2 gene is alternatively spliced but an association between genotype and splice variants has not been shown convincingly. We hypothesized that a yet unknown extra exon, containing either the C or T genotype of the SNP rs7903146, could introduce a premature stop codon and consequently result in nonsense-mediated decay (NMD).Running the sequences C and T of the SNP region in different servers we found that the two alleles could display differential recognition by splicing factors. The C variant showed the possible inclusion of an unknown exon. This unknown exon contained a stop codon and thus could induce NMD. We then determined that the splicing pattern in isolated mouse islets and MIN6 cells was similar to that in human pancreatic islets. Therefore, we used MIN6 cells to study the splicing of human intron 4: two mini-genes of intron 4 containing either the C/C genotype or the T/T genotype were transfected into MIN6 cells. Our constructs were spliced normally, excluding intron 4, but we did not observe the presence of an extra exon with either construct.We found that an extra exon could theoretically exist, although we were not able to capture it in our model. A better model is needed to determine whether a theoretical extra exon can induce NMD.

TCF7L2

Nonsense-Mediated Decay

SNP

10.1186/2193-1801-3-41

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Isomer-specific effects of conjugated linoleic acid on HDL functionality associated with reverse cholesterol transport

The Journal of Nutritional Biochemistry (2014)

Nathalie Nicod Robert S. Parker Elena Giordano Virginia Maestro Alberto Dávalos

Reverse cholesterol transport

10.1016/j.jnutbio.2014.10.002

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Challenge to evaluate regulatory compliance for nutrients in infant formulas with current state-of-the-art analytical reference methods

Food Control (2020)

Erik J M Konings Antoine Roux Audrey Reungoat Nathalie Nicod Esther Campos-Giménez

Infant formulas are strictly regulated and rigorously tested for compliance. Recently, new official analytical methods/standards have been established for nutrient analyses in these product categories through the Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN), governed by AOAC INTERNATIONAL. Many of these methods have been adopted or are in the process of being adopted as reference methods by Codex Alimentarius. The purpose of this paper is to assess the ability of these cutting-edge analytical methods to deliver acceptable results in the context of established regulatory limits for nutrients in food standards and regulations. For this evaluation, the analytical method variability is considered as one of the three main sources of overall process variability, which also includes variation in raw materials/ingredients and the manufacturing process. The process capability (Cp) is a concept for determining the overall process variability relative to specification limits for a parameter in the final product. Based on this principle an analytical method capability (Cm) was defined and calculated for SPIFAN methods. Global regulatory requirements were evaluated including minimum and maximum limits and tolerances from the declared label values. Compared to these requirements, analytical methods for vitamins A, B12, D and folic acid are of particular concern in relation to the requirements in China, some EU member states, Pakistan, Russia, Singapore, South Africa and Thailand. For a product with a manufacturing target at the midpoint of the regulatory range for these nutrients, the probability of obtaining an analytical result outside the regulatory requirements due to analytical variation alone can be as high as 19%. This does not consider variability caused by the production process and/or raw materials/ingredients. These currently used analytical methods are state-of-the-art and represent the latest developments in technology. However, this work demonstrates that continuous method improvements for the nutrients identified must be pursued. In addition, this work supports a risk management approach that takes into consideration analytical method capability when establishing regulatory limits for nutrients in infant formulas. Ongoing efforts towards harmonization of regulatory requirements across global markets will facilitate evaluation of regulatory compliance in infant formulas.

10.1016/j.foodcont.2020.107423

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Citations (11)

Hydroxytyrosol prevents hepatic endoplasmic reticulum stress in physiological concentrations

The FASEB Journal (2013)

Elena Giordano Alberto Dávalos Nathalie Nicod Francesco Visioli

Olive oil is the essential component of the Mediterranean diet, which is associated with a lower incidence of chronic diseases and higher life expectancy. Hydroxytyrosol (HT) is a phenolic compound peculiar to olives and, hence, to virgin olive oil. Among the numerous health‐promoting properties of HT, recent findings demonstrated its ability to prevent LDL oxidation which may, ultimately, decrease cardiovascular risk. One rising risk factor for cardiovascular disease is endoplasmic reticulum (ER) stress. The roles played by the ER in cardiometabolism are likely to be relevant and manifold; mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. We report the preventive activities of HT physiological concentrations toward ER stress in hepatocytes, as shown by real time‐RT PCR and Western Blot analysis of CHOP and BiP, two main components of the unfolded protein response (UPR), which is activated upon the accumulation of misfolded proteins in the ER. The protective activities of HT were superior to those of two isoflavones mostly found in soy, i.e. genistein and daidzein and of two thiolic antioxidants, i.e. lipoic acid and glutathione. Although in vivo confirmation is required, these data add mechanistic insights on specific olive phenols, such as HT, as cardioprotective compounds. Research support: Ministerio C+I España/Marie Curie Amarout EU Programme

Hydroxytyrosol

10.1096/fasebj.27.1_supplement.636.30

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Green Tea, Cocoa, and Red Wine Polyphenols Moderately Modulate Intestinal Inflammation and Do Not Increase High-Density Lipoprotein (HDL) Production

Journal of Agricultural and Food Chemistry (2014)

Nathalie Nicod Gemma Chiva‐Blanch Elena Giordano Alberto Dávalos Robert S. Parker

Although polyphenols are often merely perceived as antioxidants, their biological activities are manifold and include anti-inflammatory actions. A new area of research on polyphenols and health concerns their putative role in cholesterol metabolism, in particular, their high-density lipoprotein-cholesterol (HDL-c)-raising potential. Indeed, some human studies showed that administration of polyphenol-rich foods such as cocoa, green tea, and extra virgin olive oil modulate and increase HDL-c concentrations. This study assessed the effects of polyphenols on intestinal inflammation, using the physiologically relevant Caco-2 Transwell model and using lipopolysaccharide (LPS) to trigger inflammation. This study also investigated the mechanisms of actions behind the proposed HDL-c-increasing effects of polyphenols. The data suggest that polyphenols (at least those from red wine, cocoa, and green tea) administered at a dietary dose moderately modulate intestinal inflammation but do not increase cholesterol secretion by intestinal cells or enhance HDL functionality. Nutraceuticals and supplements provide pharmanutritional doses that might, conversely, produce beneficial effects.

Nutraceutical

10.1021/jf500348u

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Citations (37)