Françoise Galland

Centre Hospitalier Universitaire de Dijon, Dijon, Bourgogne, France

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Publications (13)36.98 Total impact

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    ABSTRACT: It has been shown that the hepatitis C virus (HCV) core protein reduces the activity of the microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients. Experimentally, apolipoprotein-AII (apoAII), which restores triglyceride secretion altered by the HCV core protein, could be protective against HCV steatosis. On the other hand, increasing plasma concentrations of mouse apoAII in transgenic mice produced several aspects of insulin-resistance syndrome, which also is implicated in the pathogenesis of HCV steatosis. This study was designed to investigate the role of apoAII in HCV-related steatosis in humans. Sixty-five hospitalized patients with chronic HCV were included in this study to assess the effects of apoAII, body mass index (BMI), age, insulin sensibility (HOMA), and leptin level on steatosis. Steatosis was observed in 55.3% of patients. Apo-AII was significantly associated with HOMA and with leptin concentrations. In univariate analyses, age, BMI, increased leptin level, increased HOMA, and increased apoAII concentration were associated with steatosis. In multivariate analysis, steatosis was associated with apoAII concentration, age, gender, and BMI. Contrary to previous hypotheses, apoAII is not a protective factor against HCV steatosis but is significantly associated with the development of liver steatosis. The fact that the plasma levels of apoAII correlate with HOMA and leptin levels in HCV-infected patients suggests that apoAII may contribute to hepatic steatosis progression in relationship to visceral obesity, insulin resistance, and metabolism of triglyceride-rich lipoproteins.
    Digestive Diseases and Sciences 01/2008; 52(12):3431-4. · 2.26 Impact Factor
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    ABSTRACT: In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P<0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1+/-4.7 vs. 24.0+/-5.8 U/mmol, P<0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.
    Diabetes & Metabolism 01/2007; 32(6):625-31. · 2.39 Impact Factor
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    ABSTRACT: Plasma concentration of adiponectin is positively correlated with high-density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22 subjects with a wide range of plasma adiponectin, including 11 patients with metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11 normal individuals. In the 22 studied subjects, plasma adiponectin levels ranged from 2.57 to 14.44 microg/mL and apoA-I fractional catabolic rate (FCR) values ranged from 0.142 to 0.340 day(-1). A strong negative correlation was found between adiponectin and apoA-I FCR (r=-0.66, P<0.001) in the whole studied population and, to a similar extent, in patients with metabolic syndrome (r=-0.73, P=0.010) and normal subjects (r=-0.68, P=0.020), separately. In multivariable analysis, apoA-I FCR was associated negatively with adiponectin (P=0.005) and positively with HDL triglycerides/cholesterol ratio (P=0.006), but not with age, sex, body mass index (BMI), waist circumference, plasma triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I FCR and adiponectin on its own explained 43%. Our kinetic study shows a strong negative correlation between adiponectin and apoA-I FCR, which can explain the positive link between HDL cholesterol and adiponectin. This association is independent of obesity, insulin resistance, and the content of triglycerides within HDL particles. These data suggest that adiponectin may have a direct role on HDL catabolism.
    Arteriosclerosis Thrombosis and Vascular Biology 07/2006; 26(6):1364-9. · 6.34 Impact Factor
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    ABSTRACT: It has been shown that the HCV-core protein reduces the activity of microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients. The aim of our study was to investigate the influence of a functional polymorphism in the promoter region of the MTP gene (493G/T) on the development of HCV-related steatosis. Eighty-six chronic hepatitis C patients were studied to assess: the effects of body mass index, age, HCV genotype, and 493G/T MTP polymorphism on steatosis. Steatosis was observed in 39 patients (45.3%). The 493G/T MTP polymorphism were not related to the development of steatosis. The functional G/T MTP polymorphism do not seem to play any role in the development of steatosis in chronic hepatitis C.
    Molecular Genetics and Metabolism 07/2006; 88(2):196-8. · 2.83 Impact Factor
  • Journal of Gastroenterology and Hepatology 04/2006; 21(3):624. · 3.33 Impact Factor
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    ABSTRACT: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.
    HIV Clinical Trials 01/2006; 7(2):41-7. · 2.30 Impact Factor
  • Annales D Endocrinologie - ANN ENDOCRINOL. 01/2006; 67(5):399-399.
  • Annales D Endocrinologie - ANN ENDOCRINOL. 01/2006; 67(5):514-514.
  • Annales D Endocrinologie - ANN ENDOCRINOL. 01/2006; 67(5):466-466.
  • Annales D Endocrinologie - ANN ENDOCRINOL. 01/2006; 67(5):514-514.
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    ABSTRACT: The mechanisms underlying steatosis during hepatitis C virus (HCV) infection are complex and multifactorial. Obesity is a well-recognized risk factor for the development of steatosis in chronic hepatitis C infection. The aim of our study was to investigate the role of adipocytokines in HCV-related steatosis. Therefore, we hypothesized that the endocrine function of adipose tissue could be, in part, responsible for HCV-related steatosis. Seventy-one consecutive untreated chronic hepatitis C patients were studied to assess the effects of adipocytokines, body mass index (BMI), age, and HCV genotype on steatosis. We used ELISA to determine serum adiponectin, leptin, and soluble TNF receptors I and II concentrations. Steatosis was observed in 42 (59.1%) patients. BMI was significantly associated with leptin (r = 0.64; P = 0.0001) and was border significantly associated with adiponectin concentrations (r = -0.22; P = 0.06). In univariate analyses, age, HCV genotype 3, BMI, increased leptin level, increased insulin level, and decreased adiponectin concentration were associated with steatosis. In multivariate analysis, steatosis was significantly associated with low adiponectin concentration, age, HCV genotype 3, and aspartate aminotransferase (ASAT) level, whereas steatosis was not associated with leptin, insulin, and BMI. In chronic HCV patients, hypoadiponectinemia is significantly associated with the development of liver steatosis. The fact that the plasma levels of adiponectin inversely correlate with steatosis in HCV-infected subjects suggests that hypoadiponectinemia may contribute to hepatic steatosis progression and liver injury in this population. One practical implication is that therapy to increase circulating adiponectin concentration, such as overweight reduction or thiazolidinediones, provides the potential to improve steatosis in chronic hepatitis C infection.
    Journal of Clinical Endocrinology &amp Metabolism 05/2005; 90(4):2240-3. · 6.43 Impact Factor
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    ABSTRACT: In the context of HIV infection and antiretroviral therapy, adiponectin concentrations have been shown to be related to lipodystrophy, metabolic alterations and HIV-protease inhibitor (PI) use. The replacement of PI by nevirapine has improved the lipid profile of patients under antiretroviral therapy. The aim of the present study was to examine whether adiponectin concentration or insulin sensitivity level correlate with the modifications of lipid parameters after the switch of PI by nevirapine. The evolution of metabolic parameters before and after 6 months of substitution of nevirapine for protease inhibitors was evaluated in a cohort of 55 HIV-1 infected patients. Adiponectin concentration, insulin sensitivity, lipid profile, cholesterol ester transfer protein (CETP) mass concentration and triglyceride enrichment of HDL were determined before and after the replacement of PI by nevirapine. Insulin sensitivity was evaluated by the HOMA model assessment. Twenty-four weeks of treatment with nevirapine improved significantly the lipid profile with a significant reduction of apoB (from 0.98 to 0.92 g L(-1); P = 0.005) and triglyceride (from 2.02 to 1.66 mmol L(-1); P = 0.02). HDL cholesterol and apoA1 increased significantly (from 0.99 to 1.19 mmol L(-1); P = 0.001 and from 1.40 to 1.57 g L(-1); P < 0.001, respectively). The triglyceride enrichment of HDL significantly decreased after the replacement of PI by nevirapine (from 0.248 +/- 0.092 to 0.213 +/- 0.093; P = 0.003). At baseline, and after 24 weeks of nevirapine treatment, we observed significant correlations between adiponectin level and lipid parameters [(HDL-cholesterol (r = 0.66, P = 0.001 and r = 0.69, P = 0.001); triglycerides (r = -0.42, P = 0.002 and r = -0.57, P = 0.001), and triglyceride enrichment of HDL (r = -0.43, P = 0.005 and r = -0.53, P = 0.005)]. Twenty-four weeks of treatment with nevirapine did not significantly change adiponectin concentrations (from 984 to 1086 micro g L(-1), P = 0.22), CETP mass and insulin sensitivity. This study shows that even though a strong correlation was found between adiponectin and some metabolic parameters at baseline and after 24 weeks of treatment by nevirapine, the improvement of lipid profile observed after the replacement of PI by nevirapine was not in relation to the change of plasma adiponectin concentration. The significant decrease of triglyceride enrichment of HDL after the replacement of PI by nevirapine probably leads to a decreased catabolism of HDL lipoprotein, and consequently explains the increase of plasma HDL concentration observed in this study.
    European Journal of Clinical Investigation 09/2004; 34(8):569-75. · 3.37 Impact Factor
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    ABSTRACT: In type 2 diabetic patients with poor metabolic control, kinetic studies have demonstrated that LDL fractional catabolic rate (FCR) is slowed down, whereas it is normalized on insulin therapy. This study was designed to analyze whether variations in the expression of LDL receptors at the cell surface could explain the results observed in kinetic studies. LDL receptors were quantified at the surface of mononuclear cells in fresh fasting blood samples by a flow cytometry method in 21 control subjects and 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy and concomitant removal of oral antidiabetic drugs. Before insulin treatment, monocyte LDL receptor expression was reduced by 41% (6,439 +/- 2,310 vs. 10,846 +/- 2,764 receptors per monocyte, P < 0.001) in type 2 diabetic patients compared with control subjects. It increased by 57% after 3 months of insulin therapy (10,096 +/- 5,657 vs. 6,439 +/- 2,310, P < 0.01) and was similar to that observed in control subjects. Our results suggest that insulin plays an important role in the in vivo expression of LDL receptors. Moreover, modulations in the expression of LDL receptors in type 2 diabetic patients either with poor metabolic control or on insulin therapy are likely to contribute to the variations of LDL FCR demonstrated by kinetic studies under those circumstances.
    Diabetes Care 05/2003; 26(5):1540-4. · 7.74 Impact Factor