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NONALCOHOLIC FATTY LIVER DISEASE ASOCIATED TO METABOLIC SYNDROME: RELATION BETWEEN VLDL PRODUCTION AND ADIPONECTIN
Poster Sessions PO6 Lipoprotein and cholesterol metabolism
26 PO5-33
NONALCOHOLIC FATTY LIVER DISEASE ASOCIATED TO METABOLIC SYNDROME: RELATION BETWEEN VLDL PRODUCTION AND ADIPONECTIN
L. Schreier 1 , V. Zago 1 , L. Cacciagiu 1 , F. Brites 1 , M. Graffigna 2 , S. Belli 2 , H. Fainboim 3 , G. de Larranaga 3 , G. Berg 1 , O. Levalle 2 . 1 Lipid and Lipoprotein Laboratory, Clinical Biochemistry Department, Faculty of Pharmacy and Biochemistry, INFIBIOC. University of Buenos Aires. Argentina; 2 Endocrinology Division, Durand Hospital, Buenos Aires, Argentina; 3 Unit of Hepatology, Muniz Hospital, Buenos Aires, Argentina Nonalcoholic fatty liver disease (NAFLD) is considered another expression of the metabolic syndrome (MS), which comprises increased VLDL despite fat liver accumulation. Reduction in adiponectin could have an influence on triglyceride deposit in a proinflammatory environment. Objective: To evaluate VLDL production and characteristics, and its relation to adiponectin in patients with MS and NAFLD. Patients with MS with no treatment were studied by ultrasonography. Among them 24 had diagnosis consistent with NAFLD (grade 3) and 17 controls (C) presented normal hepatic ultrasonography. Lipid profile, glucose, insulin, adiponectin and free fatty acids (FFA) were measured in serum samples. VLDL was isolated at d<1.006 g/ml and its chemical composition determined. No differences were detected in LDL and HDL cholesterol, triglycerides, insulin and glucose. Adiponectin was decreased in NAFLD group: mean±SD 6372±2557 ng/ml in comparison to C: 9266±4180, p=0.036. FFA were increase in NAFLD (0.75±0.34 mM) vs C (0.51±0.17) p=0.05. VLDL in NAFLD showed high proportion of proteins at the expense of apoB (4.9±2.8 mg/dl vs 1.8±0.5) p=0.007, being evident an increase in particle number, which in turn correlated with FFA level, r=0.50 p=0.016. Decrease in adiponectin was associated to increase in FFA r=-0.39; p=0.026 and in apoB-VLDL, r=-0.44, p=0.032. Although fat accumulates in the liver of MS patients with NAFLD, an increased number of VLDL particles are secreted, promoted by high FFA flux. Decrease in adiponectin is a sign of a proinflammatory state, more pronounced in MS coexisting with fatty liver disease, and linked to VLDL overproduction/secretion
PO6 LIPOPROTEIN AND CHOLESTEROL METABOLISM PO6-34
THE ROLE OF CHROMIUM IN CARBOHYDRATE AND LIPID METABOLISM. ABSORPTION OF 51CR FROM PHARMACEUTICAL CHROMIUM COMPOUNDS IN RATS
P. Nielsen, K. Kottwitz, N. Laschinsky, R. Fischer. Department of Biochemistry and Molecular Biology II: Molecular Cell Biology/Center of Experimental Medicine/University Medical Center, Hamburg, Germany Background: Chromium (Cr(III)) is commonly regarded as an essential trace element involved in the regulation of carbohydrate and lipid metabolism via enhancement of insulin action. However, little is known on the molecular basis of chromium function in-vivo. Methods: Various 51Cr-labelled compounds were synthesized and the absorption, retention and organ distribution of 51Cr was measured in rats after oral or parenteral administration. Results: Overall, Cr is absorbed to a limited extend independently from the oral dose (0.02-20 µg Cr/rat. The absorption of Cr-picolinate (Cr-Pic), which is frequently used in food supplements, was highest (see Table). However, most of the absorbed Cr from Cr-Pic is excreted into the urine within 48 hours. Following the respective whole-body-retention curves in detail, one of the three half-lifes of Cr-Pic in rats (0.01 d, 1.3 d, 19-100
d) was rather short in comparison. The two longer half-lifes were found similar for all Cr-compounds under study indicating the storage of a small fraction of Cr in liver, muscle, fat and bone. Conclusions: The results could reflect the relative stability of the Cr-Pic complex, which may be absorbed as intact molecule and be only partly metabolized in rats. PO6-35
APOE COORDINATELY REGULATES VLDL AND HDL METABOLISM: A METABOLOMIC-LIKE STUDY
M.V. Mel’kin 1 , A. Ponthieux 2 , D. Lambert 2 , S. Visvikis-Siest 2 , G. Siest 2 , A.D. Dergunov 1 . 1 National Research Centre for Preventive Medicine, Moscow, Russia; 2 INSERM U525 - Equipe 4, EA 4003, Université Henri Poincaré, Faculte De Pharmacie, Nancy, France The plasma (P), VLDL (V) triglyceride and apoB (B) clearance rates were measured both as "mass" clearance (k1) and "within particle" clearance in three patient groups (E33, E23 and E34 phenotypes) under heparin-induced lipolysis in vivo. Before heparin, the lipid (C)- and apoE (E)-specific lipoprotein profiles were followed by capillary isotachophoresis and the displacement of apoE by exogenous apoC-III at plasma titration in vitro was measured. The k1(V) values did not differ between three groups and were significantly higher the paired k1(P) values. The k1(P) values for E33 and E23 groups were 2-fold higher compared to E34. Two-fold increase in the rate constant for VLDL triglyceride clearance within the particle in E34 group compared to E23 reflected the inhibition of lipolysis by apoE2. For E33 group: (i) the k1(V) value was negatively correlated to the size of non-displaceable apoE pool in 2E lipoprotein and to the maximal apoE sorbtion capacity for 2E and 3E lipoproteins; (ii) the k1(P) value was not associated with the apoE binding parameters; (iii) the k1(V) value was positively correlated to 4C lipoprotein and the magnitude of apoC-III removal from VLDL particle; (iv) the k1(P) value was positively correlated to the content of apoE, while negatively with apoC-III, in VLDL remnants. For E34 group, the k1(V) value was positively correlated to 11C lipoprotein and 1-7C pool. Lipolysis- and receptor-mediated TG runways seem to be mostly balanced in E33 group and VLDL TG clearance may be controlled by HDL through apoE dissociation from VLDLs and apolipoprotein accumulation within "fast" HDLs at lipolysis. PO6-36
LIPID PEROXIDATION AND VITAMIN E LEVELS IN RABBITS TREATED WITH ENALAPRIL
M. Marquez, R. Sutil, M. Torres, M. Carrizales, O. Mena, R. Valera, M. Muñoz, M. Gomez, C. Yepez, M. Leal. Department of Pharmacology, University of Carabobo, Valencia Carabobo state It has been suggested that Angiotensin-converting enzyme inhibitors exhibit an antioxidant effect. To investigate a possible effect of Enalapril (EN) on oxidant/antioxidant status 40 New Zealand white rabbits were treated for 11 weeks regarding the FASEB statement. They were divided into 5 groups: A: fed regular chow (RC); B: RC enriched 0,3%w/w cholesterol (CC); C: CC 2 weeks and then RC+EN (1 mg/kg/day); E: CC+EN and G: CC 2 weeks and then RC. Levels of thiobarbituric acid reactive species (TBARS) and lipid standardized vitamin E (VE) (HPLC) in blood were measured at 0, 2, 5, 8, and 11 weeks. Results: Hypercholesterolemic diet induced significant increase of TBARS in comparison with control A. TBARS was higher in group E than B (2,52±0,66 vs 1,12±0,33 uM p<0,004) and groups C, A and G showed no differences at the end of the study (ANOVA p<0,05). Serum VE increased in groups E and B compare to groups C,G and A (ANOVA p<0,05). VE was higher in group B than in E (p<0,004), with a correspondingly higher TBARS in group E at week 11. Conclusion: In presence of prooxidant condition, Enalapril significantly increased lipid peroxidation and attenuated the increase of vitamin E level. Grant: CDCH-UC PO6-37
TRANSPORT OF GHRELIN AND OBESTATIN IN PLASMA
E. Holmes 1 , I. Davies 2 , G. Lowe 2 , L. Ranganath 1 . 1 Clinical Chemistry, Royal Liverpool Hospital, Liverpool, UK; 2 Nutritional Science, John Moores University, Liverpool, UK Introduction: Since it’s discovery in 1999, ghrelin has emerged as a key player in central appetite regulation, and also has cardiovascular actions. Roles for ghrelin in the development of atherosclerosis have also been 77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
26 PO5-33
NONALCOHOLIC FATTY LIVER DISEASE ASOCIATED TO METABOLIC SYNDROME: RELATION BETWEEN VLDL PRODUCTION AND ADIPONECTIN
L. Schreier 1 , V. Zago 1 , L. Cacciagiu 1 , F. Brites 1 , M. Graffigna 2 , S. Belli 2 , H. Fainboim 3 , G. de Larranaga 3 , G. Berg 1 , O. Levalle 2 . 1 Lipid and Lipoprotein Laboratory, Clinical Biochemistry Department, Faculty of Pharmacy and Biochemistry, INFIBIOC. University of Buenos Aires. Argentina; 2 Endocrinology Division, Durand Hospital, Buenos Aires, Argentina; 3 Unit of Hepatology, Muniz Hospital, Buenos Aires, Argentina Nonalcoholic fatty liver disease (NAFLD) is considered another expression of the metabolic syndrome (MS), which comprises increased VLDL despite fat liver accumulation. Reduction in adiponectin could have an influence on triglyceride deposit in a proinflammatory environment. Objective: To evaluate VLDL production and characteristics, and its relation to adiponectin in patients with MS and NAFLD. Patients with MS with no treatment were studied by ultrasonography. Among them 24 had diagnosis consistent with NAFLD (grade 3) and 17 controls (C) presented normal hepatic ultrasonography. Lipid profile, glucose, insulin, adiponectin and free fatty acids (FFA) were measured in serum samples. VLDL was isolated at d<1.006 g/ml and its chemical composition determined. No differences were detected in LDL and HDL cholesterol, triglycerides, insulin and glucose. Adiponectin was decreased in NAFLD group: mean±SD 6372±2557 ng/ml in comparison to C: 9266±4180, p=0.036. FFA were increase in NAFLD (0.75±0.34 mM) vs C (0.51±0.17) p=0.05. VLDL in NAFLD showed high proportion of proteins at the expense of apoB (4.9±2.8 mg/dl vs 1.8±0.5) p=0.007, being evident an increase in particle number, which in turn correlated with FFA level, r=0.50 p=0.016. Decrease in adiponectin was associated to increase in FFA r=-0.39; p=0.026 and in apoB-VLDL, r=-0.44, p=0.032. Although fat accumulates in the liver of MS patients with NAFLD, an increased number of VLDL particles are secreted, promoted by high FFA flux. Decrease in adiponectin is a sign of a proinflammatory state, more pronounced in MS coexisting with fatty liver disease, and linked to VLDL overproduction/secretion
PO6 LIPOPROTEIN AND CHOLESTEROL METABOLISM PO6-34
THE ROLE OF CHROMIUM IN CARBOHYDRATE AND LIPID METABOLISM. ABSORPTION OF 51CR FROM PHARMACEUTICAL CHROMIUM COMPOUNDS IN RATS
P. Nielsen, K. Kottwitz, N. Laschinsky, R. Fischer. Department of Biochemistry and Molecular Biology II: Molecular Cell Biology/Center of Experimental Medicine/University Medical Center, Hamburg, Germany Background: Chromium (Cr(III)) is commonly regarded as an essential trace element involved in the regulation of carbohydrate and lipid metabolism via enhancement of insulin action. However, little is known on the molecular basis of chromium function in-vivo. Methods: Various 51Cr-labelled compounds were synthesized and the absorption, retention and organ distribution of 51Cr was measured in rats after oral or parenteral administration. Results: Overall, Cr is absorbed to a limited extend independently from the oral dose (0.02-20 µg Cr/rat. The absorption of Cr-picolinate (Cr-Pic), which is frequently used in food supplements, was highest (see Table). However, most of the absorbed Cr from Cr-Pic is excreted into the urine within 48 hours. Following the respective whole-body-retention curves in detail, one of the three half-lifes of Cr-Pic in rats (0.01 d, 1.3 d, 19-100
d) was rather short in comparison. The two longer half-lifes were found similar for all Cr-compounds under study indicating the storage of a small fraction of Cr in liver, muscle, fat and bone. Conclusions: The results could reflect the relative stability of the Cr-Pic complex, which may be absorbed as intact molecule and be only partly metabolized in rats. PO6-35
APOE COORDINATELY REGULATES VLDL AND HDL METABOLISM: A METABOLOMIC-LIKE STUDY
M.V. Mel’kin 1 , A. Ponthieux 2 , D. Lambert 2 , S. Visvikis-Siest 2 , G. Siest 2 , A.D. Dergunov 1 . 1 National Research Centre for Preventive Medicine, Moscow, Russia; 2 INSERM U525 - Equipe 4, EA 4003, Université Henri Poincaré, Faculte De Pharmacie, Nancy, France The plasma (P), VLDL (V) triglyceride and apoB (B) clearance rates were measured both as "mass" clearance (k1) and "within particle" clearance in three patient groups (E33, E23 and E34 phenotypes) under heparin-induced lipolysis in vivo. Before heparin, the lipid (C)- and apoE (E)-specific lipoprotein profiles were followed by capillary isotachophoresis and the displacement of apoE by exogenous apoC-III at plasma titration in vitro was measured. The k1(V) values did not differ between three groups and were significantly higher the paired k1(P) values. The k1(P) values for E33 and E23 groups were 2-fold higher compared to E34. Two-fold increase in the rate constant for VLDL triglyceride clearance within the particle in E34 group compared to E23 reflected the inhibition of lipolysis by apoE2. For E33 group: (i) the k1(V) value was negatively correlated to the size of non-displaceable apoE pool in 2E lipoprotein and to the maximal apoE sorbtion capacity for 2E and 3E lipoproteins; (ii) the k1(P) value was not associated with the apoE binding parameters; (iii) the k1(V) value was positively correlated to 4C lipoprotein and the magnitude of apoC-III removal from VLDL particle; (iv) the k1(P) value was positively correlated to the content of apoE, while negatively with apoC-III, in VLDL remnants. For E34 group, the k1(V) value was positively correlated to 11C lipoprotein and 1-7C pool. Lipolysis- and receptor-mediated TG runways seem to be mostly balanced in E33 group and VLDL TG clearance may be controlled by HDL through apoE dissociation from VLDLs and apolipoprotein accumulation within "fast" HDLs at lipolysis. PO6-36
LIPID PEROXIDATION AND VITAMIN E LEVELS IN RABBITS TREATED WITH ENALAPRIL
M. Marquez, R. Sutil, M. Torres, M. Carrizales, O. Mena, R. Valera, M. Muñoz, M. Gomez, C. Yepez, M. Leal. Department of Pharmacology, University of Carabobo, Valencia Carabobo state It has been suggested that Angiotensin-converting enzyme inhibitors exhibit an antioxidant effect. To investigate a possible effect of Enalapril (EN) on oxidant/antioxidant status 40 New Zealand white rabbits were treated for 11 weeks regarding the FASEB statement. They were divided into 5 groups: A: fed regular chow (RC); B: RC enriched 0,3%w/w cholesterol (CC); C: CC 2 weeks and then RC+EN (1 mg/kg/day); E: CC+EN and G: CC 2 weeks and then RC. Levels of thiobarbituric acid reactive species (TBARS) and lipid standardized vitamin E (VE) (HPLC) in blood were measured at 0, 2, 5, 8, and 11 weeks. Results: Hypercholesterolemic diet induced significant increase of TBARS in comparison with control A. TBARS was higher in group E than B (2,52±0,66 vs 1,12±0,33 uM p<0,004) and groups C, A and G showed no differences at the end of the study (ANOVA p<0,05). Serum VE increased in groups E and B compare to groups C,G and A (ANOVA p<0,05). VE was higher in group B than in E (p<0,004), with a correspondingly higher TBARS in group E at week 11. Conclusion: In presence of prooxidant condition, Enalapril significantly increased lipid peroxidation and attenuated the increase of vitamin E level. Grant: CDCH-UC PO6-37
TRANSPORT OF GHRELIN AND OBESTATIN IN PLASMA
E. Holmes 1 , I. Davies 2 , G. Lowe 2 , L. Ranganath 1 . 1 Clinical Chemistry, Royal Liverpool Hospital, Liverpool, UK; 2 Nutritional Science, John Moores University, Liverpool, UK Introduction: Since it’s discovery in 1999, ghrelin has emerged as a key player in central appetite regulation, and also has cardiovascular actions. Roles for ghrelin in the development of atherosclerosis have also been 77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey