Maud Lemoine

Publications (19)85.75 Total impact

• Article: In the shadow of HIV/AIDS: Forgotten diseases in sub-Saharan Africa: Global health issues and funding agency responsibilities.

  Maud Lemoine, Pierre-Marie Girard, Mark Thursz, Gilles Raguin
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  ABSTRACT: The HIV/AIDS pandemic has generated international solidarity, particularly with sub-Saharan Africa. The mainly vertical approach to this challenge has, however, mobilized so much attention and so many resources that other crucial public health problems, such as chronic viral hepatitis and non-communicable diseases (NCDs), have been left in the shadows. One year after the first official World Hepatitis Day launched by WHO and the first UN meeting on NCDs, the world needs a vigorous debate on a more comprehensive approach to public health challenges in developing countries.
  Journal of Public Health Policy 08/2012; 33(4):430-8. · 2.11 Impact Factor
• Article: The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.

  Fadila Benhamed, Pierre-Damien Denechaud, Maud Lemoine, Céline Robichon, Marthe Moldes, Justine Bertrand-Michel, Vlad Ratziu, Lawrence Serfaty, Chantal Housset, Jacqueline Capeau, Jean Girard, Hervé Guillou, Catherine Postic
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  ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition of excess triglycerides within liver cells, a hallmark of NAFLD, is associated with a loss of insulin sensitivity, it is not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate responsive element-binding protein (ChREBP). On a standard diet, mice overexpressing ChREBP remained insulin sensitive, despite increased expression of genes involved in lipogenesis/fatty acid esterification and resultant hepatic steatosis (simple fatty liver). Lipidomic analysis revealed that the steatosis was associated with increased accumulation of monounsaturated fatty acids (MUFAs). In primary cultures of mouse hepatocytes, ChREBP overexpression induced expression of stearoyl-CoA desaturase 1 (Scd1), the enzyme responsible for the conversion of saturated fatty acids (SFAs) into MUFAs. SFA impairment of insulin-responsive Akt phosphorylation was therefore rescued by the elevation of Scd1 levels upon ChREBP overexpression, whereas pharmacological or shRNA-mediated reduction of Scd1 activity decreased the beneficial effect of ChREBP on Akt phosphorylation. Importantly, ChREBP-overexpressing mice fed a high-fat diet showed normal insulin levels and improved insulin signaling and glucose tolerance compared with controls, despite having greater hepatic steatosis. Finally, ChREBP expression in liver biopsies from patients with nonalcoholic steatohepatitis was increased when steatosis was greater than 50% and decreased in the presence of severe insulin resistance. Together, these results demonstrate that increased ChREBP can dissociate hepatic steatosis from insulin resistance, with beneficial effects on both glucose and lipid metabolism.
  The Journal of clinical investigation 05/2012; 122(6):2176-94. · 15.39 Impact Factor
• Article: From nonalcoholic fatty liver to nonalcoholic steatohepatitis and cirrhosis in HIV-infected patients: diagnosis and management.

  Maud Lemoine, Lawrence Serfaty, Jacqueline Capeau
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  ABSTRACT: Steatosis or nonalcoholic fatty liver disease (NAFLD) is commonly associated with abdominal obesity and metabolic disorders. It may evolve to severe liver injuries including nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. HIV-infected patients are aging and face an increased prevalence of abdominal obesity and metabolic disorders. We provide here an overview of NAFLD in HIV-infected patients for a better management of these patients. Steatosis is observed in 30-40% of HIV-infected patients, associated with increased adiposity and metabolic disorders. Whereas steatosis has probably a benign prognosis, clinically silent lesions of NASH are frequent in patients undergoing liver biopsy with often fibrosis and even cirrhosis. Fibrosis severity is related to age, insulin resistance and stavudine/didanosine-based therapy. Noninvasive markers of fibrosis are useful for the management of NAFLD-suspected patients. In addition to lifestyle changes, new treatment options are emerging and need to be evaluated in these patients. Steatosis is also common in HIV-hepatitis C virus (HCV) co-infected patients and worsens fibrosis progression but does not impact on the rate of sustained virological response. HIV-infected patients are at risk of NAFLD, a silent disease that can progress to more severe liver injuries. An accurate screening of these patients should be considered to prevent harmful evolution.
  Current Opinion in Infectious Diseases 02/2012; 25(1):10-6. · 4.93 Impact Factor
• Article: Chronic intermittent hypoxia: a breath of fresh air in the understanding of NAFLD pathogenesis.

  Maud Lemoine, Lawrence Serfaty
  Journal of Hepatology 09/2011; 56(1):20-2. · 9.26 Impact Factor
• Article: [Nonalcoholic fatty liver disease].

  Maud Lemoine, Lawrence Serfaty
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  ABSTRACT: NAFLD encompasses a spectrum of liver diseases including simple steatosis and nonalcoholic steatohepatitis (NASH), which is characterized by inflammation and hepatocyte ballooning on a background of steatosis. NAFLD, the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver diseases over the last decade in developed countries as well as in low and middle-income regions owing to dramatic epidemic proportions of obesity and diabetes worldwide. While simple steatosis has mostly a benign course, NASH can lead to fibrosis, cirrhosis and hepatocellular carcinoma. Insulin resistance is considered as the cornerstone in the development of NAFLD/NASH. Liver biopsy remains the gold standard for the diagnosis of NASH. However, non-invasive markers of NASH and fibrosis represent interesting tools to identify patients with severe liver injuries. Even if insulin sensitizers and hepatoprotective agents are promising drugs, no medication has been currently approved for the treatment of NASH. Diet, exercise and control of the metabolic disorders still represent crucial therapeutic options for the management of NAFLD/NASH.
  La Presse Médicale 06/2011; 41(2):169-89. · 0.67 Impact Factor
• Article: Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: a meta-analysis.

  Pierre Deltenre, Alexandre Louvet, Maud Lemoine, Abbas Mourad, Laetitia Fartoux, Christophe Moreno, Jean Henrion, Philippe Mathurin, Lawrence Serfaty
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  ABSTRACT: Recent studies suggested that SVR rates might be lower in HCV patients with insulin resistance (IR) than in patients without IR, but the extent of the impact of IR on treatment response has not been established. We aimed to confirm the role of IR assessed by the homoeostasis model assessment (HOMA-IR) on SVR and to determine its magnitude. We performed meta-analysis of studies evaluating the impact of IR in HCV patients treated with pegylated interferon and ribavirin. Fourteen studies involving 2732 patients were included. SVR was less frequent in patients with IR than in patients without IR (mean difference: -19.6%, 95% CI: -29.9% to -9.4%, p<0.001). In sensitivity analyses according to HCV-1 patients, patients with IR also less frequently attained a SVR than patients without IR (mean difference: -13.0%, 95% CI: -22.6% to -3.4%, p=0.008). In addition, the baseline HOMA-IR index was lower in responders than in non-responders (mean difference: -0.92, 95% CI: -1.53 to -0.32, p<0.001). In sensitivity analyses restricted to HCV-1 patients, the baseline HOMA-IR index remained lower in responders than in non-responders (mean difference: -0.63, 95% CI: -1.13 to -0.14, p<0.001). HCV patients with IR have a 20% lower SVR than patients without IR. The baseline HOMA-IR index is a major determinant of SVR.
  Journal of Hepatology 04/2011; 55(6):1187-94. · 9.26 Impact Factor
• Article: Prevalence and clinical significance of Küpffer cell hyperplasia with hemophagocytosis in liver biopsies.

  Virginie Prendki, Jérôme Stirnemann, Maud Lemoine, Manuel Lohez, Nazmiye Aras, Nathalie Ganne-Carrié, Claire Larroche, Dominique Roulot, Iulia Tengher-Barna, Olivier Fain, Marianne Ziol
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  ABSTRACT: Hemophagocytic syndrome (HS) is a rare life-threatening condition due to uncontrolled macrophagic activation. Liver involvement is constant in HS, characterized by Küpffer cell hyperplasia with hemophagocytosis. Conversely, the specificity, frequency, and clinical significance of this histologic lesion remain poorly investigated. We aimed to evaluate the prevalence of this elementary lesion in liver biopsies (LB) to attempt to identify its clinical significance and to investigate its potential association with perforin expression deficiency. Küpffer cell hyperplasia with hemophagocytosis has been systematically searched for in consecutive LBs in a 6-year period. In positive cases, clinical, biological, and outcome characteristics have been retrospectively recorded. The ratio of perforin to CD3(+) lymphocytes was assessed on immunostained LB sections. This histologic lesion was detected in LB of 69 of 5194 patients (1.3%). It was not associated with hepatotropic viral infection, alcohol-related chronic liver disease, or autoimmune chronic liver disease. Although only 36% of patients with this histologic lesion had a complete HS (association of fever, splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia, and/or hypofibrinogenemia), almost all patients had similar underlying diseases (human immunodeficiency virus infection, malignant hemopathy, and autoimmune disease) and/or acute ongoing infections (tuberculosis, cytomegalovirus, and Epstein-Barr virus). A decrease of the perforin to CD3(+) lymphocytes ratio was specifically associated with this lesion. Küpffer cell hyperplasia with hemophagocytosis in LB is a rare finding; although it does not necessarily denote a complete HS, it is associated with the same underlying disease and/or infection, with a decrease in intrahepatic perforin-positive lymphocytes.
  The American journal of surgical pathology 03/2011; 35(3):337-45. · 4.06 Impact Factor
• Article: Adipokines and nonalcoholic fatty liver disease: authors' reply.

  Maud Lemoine, Jacqueline Capeau, Jean-Philippe Bastard, Lawrence Serfaty
  Liver international: official journal of the International Association for the Study of the Liver 04/2010; · 3.82 Impact Factor
• Source

  Available from: Marianne Ziol

  Article: Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: a prospective magnetic resonance imaging and histological study.

  Maïté Lewin, Valérie Vilgrain, Violaine Ozenne, Maud Lemoine, Dominique Wendum, Valérie Paradis, Marianne Ziol, Lionel Arrivé, Michel Beaugrand, Raoul Poupon, Dominique Valla, Olivier Chazouillères, Christophe Corpechot
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  ABSTRACT: The development of sclerosing cholangitis (SC) is observed in up to 50% of children followed up for autoimmune hepatitis (AIH). In adults, the prevalence is less known, although a recent study found evidence of SC in 10% of AIH patients using magnetic resonance cholangiopancreatography (MRCP). The aim of this study was to assess prospectively the prevalence of SC in adults with AIH. Fifty-nine consecutive patients with AIH diagnosed according to International Autoimmune Hepatitis Group score (women, 71%; mean age, 48 years; cirrhosis, 23%) underwent both MRCP and percutaneous liver biopsy. Twenty-seven patients with cirrhosis of nonbiliary or non-autoimmune etiology served as controls. Fourteen AIH patients (24%) showed mild MRCP abnormalities of intrahepatic bile ducts (IHBDs). None had abnormal common bile duct or convincing evidence of SC on MRCP or biopsy. A diagnosis of overlapping SC was nevertheless retained in one patient with MRCP abnormalities who subsequently developed symptomatic cholestasis despite corticosteroid therapy. Fibrosis score was the only independent parameter associated with bile duct abnormalities on MRCP (odds ratio 2.4; 95% confidence interval 1.4-4.7) and the percentage of patients with IHBD MRCP abnormalities was not different among F3-F4 AIH patients (n = 24) and cirrhotic controls (46% versus 59%; NS). CONCLUSION: In this cohort of adult patients with AIH, the prevalence of SC was much lower than previously reported (1.7%). Mild MRCP abnormalities of IHBD were seen in a quarter of patients, but these abnormalities resulted from hepatic fibrosis and not SC. In the absence of cholestatic presentation, MRCP screening does not seem justified in adult-onset AIH.
  Hepatology 09/2009; 50(2):528-37. · 11.66 Impact Factor
• Article: Enzymatic degradation of κ-carrageenan in aqueous solution.

  Pi Nyvall Collén, Maud Lemoine, Richard Daniellou, Jean-Paul Guégan, Sergio Paoletti, William Helbert
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  ABSTRACT: Enzymatic degradation of standard κ-carrageenan and the low-gelling hybrid κ-/μ-carrageenan were conducted using recombinant Pseudoalteromonas carrageenovora κ-carrageenase. The initial velocity of the enzyme was determined as a function of varying Tris or NaI concentrations and at constant 200 mM cosolutes concentration, adjusting NaI and Tris concentrations accordingly. In both cases, we observed strong inhibition of the enzyme with increasing amounts of iodide. The characterization of the κ- and κ-/μ-carrageenan ordering by optical rotation and the visualization of iodide binding on carrageenan by (127)I NMR revealed that inhibition was not caused by the disordered-ordered transition of carrageenan in NaI, but by iodide binding. These results were confirmed by analysis of the degradation products by gel permeation chromatography. Degradation of carrageenan in the disordered state led to a rapid decrease in molecular mass and the production of all possible neo-κ-carrabiose oligomers. In the ordered conformation, the degradation kinetics, the decrease of average molecular weight, and the chain population distribution of degradation products varied with iodide concentration. These observations were interpreted to be the result of increasing amounts of bound iodide on carrageenan helices that, in turn, impede enzyme catalysis. Based on these results, we propose a single-helix ordered conformation state for κ-carrageenan and reject the previously advocated double-helix model.
  Biomacromolecules 06/2009; 10(7):1757-67. · 5.48 Impact Factor
• Article: Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease.

  Maud Lemoine, Vlad Ratziu, Minji Kim, Mustapha Maachi, Dominique Wendum, François Paye, Jean Philippe Bastard, Raoul Poupon, Chantal Housset, Jacqueline Capeau, Lawrence Serfaty
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  ABSTRACT: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients with non-alcoholic fatty liver disease (NAFLD). Fifty-seven patients with biopsy-proven non-alcoholic steatohepatitis (NASH) (mean age 51+/-12, sex ratio 1), 17 with simple steatosis (mean age 47+/-12, sex ratio 1.4) and 10 controls without steatosis (mean age 51+/-11, sex ratio 4) were investigated. In all subjects, serum concentrations of triglycerides, ultrasensitive C reactive protein, leptin, adiponectin, soluble tumour necrosis factor receptor 1, interleukin (IL)-6 and Homeostasis Model Assessment Method (HOMA) were measured. Hepatic expression of adiponectin and its two receptors was assessed by quantitative reverse transcriptase polymerase chain reaction. Body mass index (BMI) and HOMA were correlated positively with leptin levels (r=0.44 and 0.28 respectively) and negatively with the A/L ratio (r=0.51 and 0.41 respectively). Independent parameters associated with NASH vs steatosis were HOMA>3 [odds ratio (OR)=6.9] and A/L ratio <1.4 10(3) (OR=5.2). The combination of HOMA with A/L ratio showed an area under the receiver operating characteristic curve of 0.82 for distinguishing between NASH and steatosis. Extensive portal fibrosis was present in 17 (23%) patients with NAFLD. Three independent parameters were associated with fibrosis: age (OR=1.1), BMI (OR=1.3) and high IL-6 levels (OR=1.6). The hepatic expression of adiponectin receptor 2 was significantly higher in patients with NASH compared with controls and was related with necroinflammatory injury. This study shows that in patients with NAFLD, the combination of HOMA with A/L ratio may be a useful non-invasive approach to appreciate the severity of liver damage.
  Liver international: official journal of the International Association for the Study of the Liver 04/2009; 29(9):1431-8. · 3.82 Impact Factor
• Source

  Available from: cnrs.fr

  Article: Physical state of kappa-carrageenan modulates the mode of action of kappa-carrageenase from Pseudoalteromonas carrageenovora.

  Maud Lemoine, Pi Nyvall Collén, William Helbert
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  ABSTRACT: Pseudoalteromonas carrageenovora kappa-carrageenase is a glycoside hydrolase involved in the bioconversion of carrageenans. Carrageenans are sulfated galactans that are densely packed in red algal cell walls. Previous crystallographic investigations revealed that the active site of kappa-carrageenase has a tunnel-shaped topology, suggesting a processive mode of action for this enzyme. To biochemically characterize the enzymatic depolymerization of kappa-carrageenan, soluble and solid substrates (in both gel and powder forms) were incubated with P. carrageenovora kappa-carrageenase. The average molecular mass of soluble carrageenan decreased rapidly, and all possible degradation products were observed, suggesting random degradation of kappa-carrageenan. In contrast, as expected for a processive-type carrageenase, the average molecular mass of solid carrageenan decreased very slowly, and tetrasaccharide production was high. Interestingly, experimentally determined processivity was similar for gel and powder, suggesting that, in addition to an adapted catalytic site, the substrate must be in the solid state for kappa-carrageenase processivity to operate, whatever the level of carrageenan ordering.
  Biochemical Journal 03/2009; 419(3):545-53. · 4.90 Impact Factor
• Article: Liver stiffness measurement in patients with cirrhosis and hepatocellular carcinoma: a case-control study.

  Pierre Nahon, Adrien Kettaneh, Maud Lemoine, Olivier Seror, Nathalie Barget, Jean-Claude Trinchet, Michel Beaugrand, Nathalie Ganne-Carrié
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  ABSTRACT: A wide range in values of liver stiffness measurement (LSM) is observed among cirrhotic patients. These variations reflect the extent of fibrosis and might influence the risk of hepatocellular carcinoma (HCC) occurrence. We compared LSM in 66 Child-Pugh A patients with HCC and alcoholic (n=23) or HCV-related cirrhosis (n=43) referred for radiofrequency ablation and in 199 Child-Pugh A with alcoholic (n=69) or HCV-related cirrhosis (n=130) without HCC. Patients with HCC had higher LSM than patients without HCC [35.3 kPa (22.8-52.6) vs. 19.0 kPa (12.4-29.2), P<0.0001]. In multivariate analysis, HCC was associated with higher LSM [odds ratio=1.051 (1.030-1.072) (by 1 kPa increase), P<0.0001] and with age [odds ratio=1.075 (1.043-1.107) (by 1 year increase), P<0.0001]. In patients without HCC, LSM was not correlated with age but with decreased prothrombin activity, serum albumin, platelet count, and increased serum bilirubin level. Alcoholic patients had higher LSM compared with HCV-infected patients [22.1 kPa (14.0-36.5) vs. 15.9 kPa (10.8-21.9), P<0.0001] and LSM in the latter varied according to antiviral treatment response. In patients with Child-Pugh A cirrhosis, a wide range of LSM is observed according to the cause underlying liver disease and the presence of HCC is associated with higher values in these patients.
  European journal of gastroenterology & hepatology 02/2009; 21(2):214-9. · 1.66 Impact Factor
• Source

  Available from: Laurent Dubuquoy

  Article: Peroxisome proliferator-activated receptors in HCV-related infection.

  Sébastien Dharancy, Maud Lemoine, Philippe Mathurin, Lawrence Serfaty, Laurent Dubuquoy
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  ABSTRACT: The topic of peroxisome proliferator-activated receptors has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases such as chronic infection with hepatitis C virus (HCV). PPARs contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differentiation, and cell cycle. In vitro experiments and animal studies showed that PPARα discloses anti-inflammatory property, and PPARγ discloses anti-inflammatory, antifibrogenic, and antiproliferative properties in the liver. Experimental and human studies showed impaired PPARs expression and function during HCV infection. The available nonhepatotoxic agonists of PPARs may constitute a progress in the therapeutic management of patients chronically infected with HCV.
  PPAR Research 02/2009; 2009:357204.
• Source

  Available from: PubMed Central

  Article: PPAR and liver injury in HIV-infected patients.

  Maud Lemoine, Jacqueline Capeau, Lawrence Serfaty
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  ABSTRACT: Due to the introduction of active HIV antiretroviral treatment, AIDS-related morbidity and mortality have markedly decreased and liver diseases are now a major cause of morbidity and mortality in HIV-infected patients. Chronic liver injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection, drug-related toxicity, and NASH. HIV-infected patients who are receiving treatment present with a high prevalence of metabolic complications and lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver disease, the liver feature of the metabolic syndrome. This review will focus on (1) the liver injuries in HIV-infected patients; (2) both the current experimental and human data regarding PPAR and liver diseases; (3) the interactions between HIV and PPAR; (4) the potential use of PPAR agonists for the management of HIV-related liver diseases.
  PPAR Research 02/2009; 2009:906167.
• Article: Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus.

  Maud Lemoine, Aurelie Revaux, Claire Francoz, Guillaume Ducarme, Sabine Brechignac, Emmanuel Jacquemin, Michele Uzan, Nathalie Ganne-Carrie
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  ABSTRACT: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.
  World Journal of Gastroenterology 12/2008; 14(42):6572-4. · 2.47 Impact Factor
• Article: [Polysaccharides enzymatic degradation in heterogeneous phase: example of agarases and carrageenases].

  Maud Lemoine, William Helbert
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  ABSTRACT: Agars and carrageenans are sulphated galactans which assemble in the red algal cell wall as a dense network of semi-crystalline fibers. These polysaccharides are degraded in heterogeneous phase by bacterial enzymes, namely agarases and carageenases. Crystallographic as well as enzymologic investigations of the sulphated galactans/galactanases systems highlight that the properties of these catalysts are well adapted to the degradation of solid polyanionic substrates. Indeed, as for cellulases or amylases, they are able to depolymerize their respective substrates according to a processive mode of action. However, at the molecular level, they are distinguished by the ionic nature of the interactions involved which do not allow the direct transposition of the processivity models developed for the degradation of neutral polysaccharides.
  Journal de la Société de Biologie 02/2007; 201(3):291-6.
• Article: Altered hepatic expression of SREBP-1 and PPARgamma is associated with liver injury in insulin-resistant lipodystrophic HIV-infected patients.

  Maud Lemoine, Véronique Barbu, Pierre Marie Girard, Minji Kim, Jean-Philippe Bastard, Dominique Wendum, François Paye, Chantal Housset, Jacqueline Capeau, Lawrence Serfaty
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  ABSTRACT: HIV-infected patients with HAART-related lipodystrophy are frequently insulin resistant and at risk of non-alcoholic fatty liver disease (NAFLD) with steatohepatitis (NASH). The transcription factors, peroxisome proliferator activated receptors (PPARalpha, PPARgamma1/PPARgamma2) and sterol regulatory element binding proteins (SREBP-1) regulate liver lipid metabolism. Here, we examined whether their expression was modified and related to liver injury in HIV-infected patients. Fourteen HAART-treated HIV patients (nine with and five without insulin resistance) who had liver biopsy because of unexplained elevated transaminases were compared with nine non-HIV age-and body mass index-matched patients with NAFLD and 10 controls without steatosis. Hepatic expression of PPARs and SREBP-1 was assessed by real time reverse transcriptase-polymerase chain reaction. Liver histology showed NASH in six of nine insulin-resistant lipodystrophic and two of five non-insulin-resistant HIV patients. Compared with NAFLD or control subjects, expression of SREBP-1 was significantly higher only in HIV-insulin-resistant patients (P = 0.04 and P = 0.02) whereas, compared to controls, HIV-insulin-resistant, HIV-non-insulin-resistant and NAFLD patients had lower expressions of PPARgamma1 (P = 0.03, P = 0.05 and P = 0.01) and PPARgamma2 (P = 0.04, P = 0.05 and P = 0.01). Among HIV patients, the percentage of steatosis was positively correlated with SREBP-1 expression (r = 0.62, P = 0.04) whereas the score of fibrosis was inversely correlated with PPARgamma1 and PPARgamma2 expression (r = -0.57, P = 0.03 and r = -0.6, P = 0.02, respectively). Insulin-resistant lipodystrophic HIV-infected patients may develop NASH. Steatosis is associated with overexpression of SREBP-1 and fibrosis with decreased expression of PPARgamma1 and PPARgamma2. These results suggest that altered expression of SREBP-1 and PPARgamma could contribute to the pathogenesis of steatosis and fibronecrotic changes in insulin-resistant lipodystrophic patients.
  AIDS 03/2006; 20(3):387-95. · 6.24 Impact Factor
• Article: Dégradation enzymatique en phase hétérogène des polysaccharides : exemple des agarases et des carraghénases

  Maud Lemoine, William Helbert
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  ABSTRACT: Agars and carrageenans are sulphated galactans which assemble in the red algal cell wall as a dense network of semi-crystalline fibers. These polysaccharides are degraded in heterogeneous phase by bacterial enzymes, namely agarases and carageenases. Crystallographic as well as enzymologic investigations of the sulphated galactans/galactanases systems highlight that the properties of these catalysts are well adapted to the degradation of solid polyanionic substrates. Indeed, as for cellulases or amylases, they are able to depolymerize their respective substrates according to a processive mode of action. However, at the molecular level, they are distinguished by the ionic nature of the interactions involved which do not allow the direct transposition of the processivity models developed for the degradation of neutral polysaccharides. Les agars et les carraghénanes sont des galactanes sulfatés qui s'assemblent dans la paroi des algues rouges sous la forme d'un réseau dense de fibres semicristallines. Ces polysaccharides sont dégradés en phase hétérogène par des enzymes bactériennes : les agarases et les carraghénases. Les études cristallographiques et enzymologiques des systèmes galactanes sulfatés/galactanases ont permis de mettre en lumière que ces enzymes possèdent des propriétés adaptées à la dégradation de substrats solides polyanioniques. En effet, à l'instar des cellulases et amylases, elles sont capables de dépolymériser leur substrat respectif selon un mode d'action processif. Cependant, les galactanases se distinguent au niveau moléculaire par la nature des interactions avec le substrat. Elles sont de type ionique, ce qui ne permet pas de transposer directement les modèles de processivité développés dans les cas de la dégradation des polysaccharides neutres.
  http://dx.doi.org/10.1051/jbio:2007027.