Federation dEndocrinologie

Sainte-Foy-lès-Lyon, France

Federation dEndocrinologie

Sainte-Foy-lès-Lyon, France
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Charriere S.,Federation dEndocrinologie | Charriere S.,INSA Lyon | Peretti N.,Hopital Femme Mere Enfant | Peretti N.,INSA Lyon | And 13 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: GPIHBP1 is a new endothelial binding site for lipoprotein lipase (LPL), the key enzyme for intravascular lipolysis of triglyceride-rich lipoproteins (TGRL).Wehave identified two new missense mutations of the GPIHBP1 gene, C89F and G175R, by systematic sequencing in a cohort of 376 hyperchylomicronemic patients without mutations on the LPL, APOC2, or APOA5 gene. Objective: Phenotypic expression and functional consequences of these two mutations were studied. Design: We performed clinical and genotypic studies of probands and their families. GPIHBP1 functional alterations were studied in CHO pgsA-745 transfected cells. Results: Probands are an adult with a homozygous G175R mutation and a child with a hemizygous C89F neomutation and a deletion of the second allele. C89F mutation was associated with a C14F signal peptide polymorphism on the same haplotype. Both patients had resistant hyperchylomicronemia, low LPL activity, and history of acute pancreatitis. In CHOpgsA-745 cells, both G175R and C14F variants reduce the expression of GPIHBP1 at the cell surface. C89F mutation is responsible for a drastic LPL-binding defect to GPIHBP1. C14F may further potentiate C89F effect. Conclusions: The emergence of hyperchylomicronemia in the generation after a neomutation further establishes a critical role for GPIHBP1 in TGRL physiopathology in humans. Our results highlight the crucial role of C65-C89 disulfide bond in LPL binding by GPIHBP1 Ly6 domain. Furthermore, we first report a mutation of the hydrophobic C-terminal domain that impairs GPIHBP1 membrane targeting. Copyright © 2011 by The Endocrine Society.


Cugnet-Anceau C.,University Claude Bernard Lyon 1 | Cugnet-Anceau C.,INSA Lyon | Cugnet-Anceau C.,French Institute of Health and Medical Research | Cugnet-Anceau C.,French National Institute for Agricultural Research | And 21 more authors.
British Journal of Nutrition | Year: 2010

Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control. The present work aims at analysing the effects of the enrichment of a normal diet with β-glucan (35g/d) in free-living type 2 diabetic subjects for 2 months, using a palatable soup. This trial was a parallel, placebo-controlled, double-blinded randomised study performed in fifty-three type 2 diabetic subjects. During a 3-week run-in period, subjects daily consumed a ready meal control soup (without β-glucan). For the following 8 weeks, subjects were randomly assigned to consume daily either a control soup or a β-glucan soup. Changes in lipid profile (total cholesterol (TC), HDL-and LDL-cholesterol (HDLc and LDLc), apo B and TAG) and in glucose control (HbA1c and fasting glucose) were measured. There was no significant alteration in lipid profile in the two groups (TC, HDLc, LDLc and apo B). TAG decreased significantly in the β-glucan group compared with the control group (012 (sd 038) v. 012 (sd 044)mmol/l, P=003). HbA1c and fasting glucose were not reduced in any group. A single daily ingestion of 35g β-glucan, as required by official dietary recommendations, for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects. To improve the metabolic profile of type 2 diabetic subjects in the long term, the quantity, the food vectors and the tolerability of β-glucan products may be re-evaluated.


Di Filippo M.,UF Dyslipidemies Cardiobiologie | Di Filippo M.,INSA Lyon | Moulin P.,INSA Lyon | Roy P.,Service de Biostatistique | And 30 more authors.
Journal of Hepatology | Year: 2014

Background & Aims: Non-alcoholic steatohepatitis leading to fibrosis occurs in patients with abetalipoproteinemia (ABL) and homozygous or compound heterozygous familial hypobetalipoproteinemia (Ho-FHBL). We wanted to establish if liver alterations were more frequent in one of both diseases and were influenced by comorbidities. Methods: We report genetic, clinical, histological and biological characteristics of new cases of ABL (n = 7) and Ho-FHBL (n = 7), and compare them with all published ABL (51) and Ho-FHBL (22) probands. Results: ABL patients, diagnosed during infancy, presented mainly with diarrhea, neurological and ophthalmological impairments and remained lean, whereas Ho-FHBL were diagnosed later, with milder symptoms often becoming overweight in adulthood. Despite subtle differences in lipid phenotype, liver steatosis was observed in both groups with a high prevalence of severe fibrosis (5/27 for Ho-FHBL vs. 4/58 for ABL (n.s.)). Serum triglycerides concentration was higher in Ho-FHBL whereas total and HDL-cholesterol were similar in both groups. In Ho-FHBL liver alterations were found to be independent from the apoB truncation size and apoB concentrations. Conclusions: Our findings provide evidence for major liver abnormalities in both diseases. While ABL and Ho-FHBL patients have subtle differences in lipid phenotype, carriers of APOB mutations are more frequently obese. These results raise the question of a complex causal link between apoB metabolism and obesity. They suggest that the genetic defect in VLDL assembly is critical for the occurrence of liver steatosis leading to fibrosis and shows that obesity and insulin resistance might contribute by increasing lipogenesis. © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


D'Herbomez M.,Lille 2 University of Health and Law | Do Cao C.,Center Hospitalier Of Lille | Vezzosi D.,Service dendocrinologie | Borzon-Chasot F.,Federation dendocrinologie | Baudin E.,Institute Gustave Roussy
Annales d'Endocrinologie | Year: 2010

Chromogranins belong to the family of secretory chromogranin and secretogranin proteins. They are found in secretory vesicles throughout the neuroendocrine system. Chromogranin A (CgA) is the main component. CgA acts as a prohormone submitted to processes of degradation through which active peptides are generated. CgA has auto, para and endocrine functions. It is widely used as an immunohistochemical marker. Despite the lack of international standardization, and the lack of an accurate definition of the diagnostic cut-off levels, some CgA assays are reliable. Numerous studies have suggested that CgA determination may be of interest for the diagnosis and the follow-up of various endocrine tumors. Plasma levels of this general marker are proportional to tumor mass. The localization of the primitive tumor, the presence of associated hormonal secretions and possible renal failure and/or hypergastrinemia must be taken into consideration for proper interpretation of CgA levels. New clinical indications are emerging for the evaluation of stress in intensive care units and the assessment of cardiovascular risk. New assays estimating the concentration of active peptides are under development. © 2010 Elsevier Masson SAS.


Caussy C.,Federation dEndocrinologie | Caussy C.,University Claude Bernard Lyon 1 | Charriere S.,Federation dEndocrinologie | Charriere S.,University Claude Bernard Lyon 1 | And 9 more authors.
American Journal of Human Genetics | Year: 2014

APOA5 c.*158C>T (rs2266788), located in the 3′ UTR, belongs to APOA5 haplotype 2 (APOA5*2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5*2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5*2 could involve miRNA regulation in the APOA5 3′ UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3′ UTR with the c.*158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3′ UTR luciferase reporter vector and a miR485-5p precursor, c.*158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.*158C allele than in the presence of the c.*158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.*158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5*2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p. © 2014 The American Society of Human Genetics.


Le Q.H.,University Claude Bernard Lyon 1 | El Alaoui M.,CNRS Institute of Molecular and Supramolecular Chemistry and Biochemistry | Vericel E.,University Claude Bernard Lyon 1 | Segrestin B.,Federation dEndocrinologie | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: High-density lipoproteins (HDL) possess atheroprotective properties including antithrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). Objective: The objective of our study was to investigate the effects of in vitro glycoxidized HDL and HDL from patients with T2D on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Results: Compared with control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to scavenger receptor BI (SR-BI). Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phosphatidylcholine (PC), namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE, and 15-HETE in phospholipids (2.1-, 2.1-, and 2.4-fold increase, respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Conclusions: Our results suggest that in vitro glycoxidized HDL as well as HDL from patients with T2D inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from patients with T2D. Copyright © 2015 by the Endocrine Society.


Background: The iodine status of the French population has been improved since 1952. As iodine requirements increase during pregnancy, the World Health Organization recommended in 2005 systematic iodine supplementation for pregnant women. Our work tried to assess the benefits and risks of iodine supplementation during pregnancy. Methods: We reviewed the international literature from 1991 to 2011 and consulted the main references databases. Keywords were combined with boolean operators AND and OR. Selected studies were assessed with Consort grid. Results: Among 226 papers, 99 were original articles. After analysis, 13 studies were included in this review. A favorable trend toward iodine supplementation from pregnancy desire to the end of pregnancy was observed. Iodine supplementation may prevent psychomotor and neuro-intellectual disorders. Conclusion: Iodine status of pregnant women could be improved before pregnancy by more widespread use of iodized salt and iodine-enriched bread in French households. A randomized controlled trial is recommended to confirm the benefit of iodine supplementation. © 2013 Elsevier Masson SAS.


PubMed | Federation dendocrinologie and University of Lyon
Type: Journal Article | Journal: Revue d'epidemiologie et de sante publique | Year: 2014

The iodine status of the French population has been improved since 1952. As iodine requirements increase during pregnancy, the World Health Organization recommended in 2005 systematic iodine supplementation for pregnant women. Our work tried to assess the benefits and risks of iodine supplementation during pregnancy.We reviewed the international literature from 1991 to 2011 and consulted the main references databases. Keywords were combined with boolean operators AND and OR. Selected studies were assessed with Consort grid.Among 226 papers, 99 were original articles. After analysis, 13 studies were included in this review. A favorable trend toward iodine supplementation from pregnancy desire to the end of pregnancy was observed. Iodine supplementation may prevent psychomotor and neuro-intellectual disorders.Iodine status of pregnant women could be improved before pregnancy by more widespread use of iodized salt and iodine-enriched bread in French households. A randomized controlled trial is recommended to confirm the benefit of iodine supplementation.


Colas R.,INSA Lyon | Sassolas A.,INSA Lyon | Guichardant M.,INSA Lyon | Cugnet-Anceau C.,Federation Dendocrinologie | And 4 more authors.
Diabetologia | Year: 2011

Aims/hypothesis: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. Methods: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. Results: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A2, and through increased thromboxane B2 formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. Conclusions/interpretation: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation. Trial registration:: ClinicalTrials.gov NCT00932087 Funding:: The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and ANR (Agence Nationale de la Recherche). © 2011 Springer-Verlag.

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