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W08-O-002 Decreased adiponectin levels in patients with familial combined hyperlipidemia
Workshops W8 Visceral fat, adipocytolcines and cardiovascular risk TG (retool/l) affected 1.54+0.67 unaffected 0.95 4- 0.39 (mean + S.D.)
HDL-C (mmol/I) 0.96+0.23 1.594- 0.47
LDL-C ApoA 1 (retool/I) (rag/all) 3.024-0.86 1124-13.9 2.81 4- 0.90 148 4- 23.5
ApoB (mg/dl) 103.84-25.5 86.6 4- 27.0
Conclusions: Smaller and potentially less protective HDL particles predominate in the fasting serum of the affected low HDL family members.
W8
V I S C E R A L FAT, A D I P O C Y T O K I N E S A N D C A R D I O V A S C U L A R RISK
W08-1S-001 J ADIPONECTIN AND THE M E T A B O L I C SYNDROME S.M. Brichard. Unit of Endocrinology and Metabolism, Faculty of Medicine, University of Louvain, UCL 5530, 55 Avenue Hippocrate, B-1200 Brussels, Belgium Adipose tissue secretes a large number of physiologically active peptides that often share structural properties with adipocytokiues, and are therefore referred to as adipocytokiues. Two adipecytokiues, leptin and adiponectin (ApN) exert major metabolic properties in mice. Their altered circulating profile may play a determinant role in the pathogenesis of human obesity and its related metabolic disorders (metabolic syndrome). ApN seems to he the most promising therapeutic target. This 247 aminoacid peptide is composed of an N-terminal collagenous domain and a C-terminal globular domain. In addition to full-length protein, the globular fragment (gApN), generated by proteolysis, may exhibit some activity. Full-length or proteolytic fragments of ApN exert hypolipemic, anti-diabetic, and perhaps anti-obesity properties (at least when energy intake is controlled) in mice. ApN also prevents the development of atherosclerosis and displays anti-inflammatory effects. Two types of adiponectin receptors are thought to mediate the metabolic effects of the hormone via stimulation of AMPK, PPARalpha and p38 MAPK. AdipoR1, which is a high-affinity receptor for gApN, is most abundantly expressed in skeletal muscle, while adipoR2, which serves as a moderute-affinity receptor for both forms of ApN, is predominant in liver. Circulating levels of ApN are paradoxically decreased in obesity and the metabolic syndrome. These low levels may have potential repercussions in the pathophysiology of this syndrome. This deficiency also raises the opportunity of a potential therapeutic supplementation. /
W08-1S-002 | THE ADIPOSE TISSUE AS AN ENDOCRINE ORGAN: IMPLICATION IN I N F L A M M A T I O N AND ATHEROSCLEROSIS M. Guerre-Millo. U465 INSERM, Paris France White adipose tissue 0NAT) produces a variety of bioactive peptides acting locally (autocrine/paracrine) or released into the blood stream to reach distant targets (endocrine). Alteration of WAT mass in obesity or lipoatrophy affects the production of most adipose secreted factors (termed "adipokines"). Since both conditions are associated with multiple metabolic disorders and increased risk of cardiovascular diseases, the idea has emerged that WAT could be instrumental in these complications by virtue of its secreted factors. Several adipokiues are increased in the obese state and have been implicated in obesity-linked hypertension (angiotensinogen), impaired fibrinolysis (PAl-I) and insulin resistance ('I'NFc~, IL-6, resistin). Leptin and adiponectin both exert an insalin-sensitizing effect, at least in part by favoring tissue fatty-acid oxidation through activation of AMP-activated kinase (AMPK). In obesity, leptin resistance coupled with decreased plasma adiponectin favor insulin resistance. Beside their common insulin-sensitizing effect, leptiu and adiponectin have distinct properties, leptin, as a long-term integrative signal of energy store and adiponectin, as a potent anti-atherogenic agent. Thus, through its secretory function, WAT lies at the heart of a complex network of factors capable of influencing several physiological processes. The possibility now exists to develop drugs targeting adipose secreted factors, representing a new approach to sensitize peripheral tissues to insulin and protect patients from atherosclerosis.
29
W08-O-001 ] FAMILIAL H Y P E R C H O L E S T E R O L E M I A PATIENTS W I T H CORONARY ARTERY DISEASE T. Bouhali 1, D. Brisson 1, G. Tremblay 1, C. Gagne 2, P. Couture 2, M.N. Vissers 3, B.A. Hutten 3, J.J. Kastelein 3, D. Gaudet I . 1Lipid Clinic
and CMGC, Chicoutimi Hospital, Chicoutimi, Canada, 2 CRMI~ Laval University Hospital, Quebec, Canada, 3 Depts. of Vascular Medicine and Clinical Epidemiology-Biostatistics, U. of Amsterdam, the Netherlands Familial hypercholesterolemia (FH) represents a major susceptibility phenotype for premature coronary artery disease (CAD) that frequently occurs in subjects under fifty. However, some FH eider subjects never developed CAD, even without treatment or appropriate diet. HDL-Cholesterol levels have been previously associated with a modulation of CAD risk in FH. The strong correlation between plasma HDL-Cholesterol and adiponectin levels, and the anti-inflammatory anti-atherogenic properties of the latter, suggest that adiponectin could also he involved in CAD risk modulation among FH. Objective: To examine the relationship between plasma adiponectin levels and age at the first CAD event in FH patients. Methods: Adiponectin concentrations were measured by Elisa, in a sample of 172 heterozygous French Canadian FH patients. Proportional hazard model and the tertiles of adiponectin levels were used. Results: Increased plasma adiponectin concentrations were associated with longer survival without CAD, independently of other covariates and even after an adjustment for HDL-Cholesterol (p = 0.004). Conclusion: Plasma adiponectin levels are associated with a reduction of premature CAD risk in FI-I, independently of known CAD risk modulators. The present results reinforce the idea that adiponectin could he a new promising therapeutic target in CAD prevention.
W08-O-002 ] DECREASED A D I P O N E C T I N LEVELS IN PATIENTS W I T H FAMILIAL COMBINED HYPERLIPIDEMIA G.M. van der Vleuteu L.J.H. van Tits, M. den Heijer, H.L.M. Hak-Lemmers, A.F.H. Stalenhoef, J. de Graaf. General Internal
Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Objective: Familial combined hypedipidemia (FCH) is characterized by hypercholesterolemia and/or hypeariglyceridemia and premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Adiponectiu is a secretory product of the adipose tissue. Low levels of adiponectin contribute to insulin resistance and are associated with accelerated atherogenesis. The aim of this study is to determine whether decreased adiponectin levels contribute to the FCH phenotype and its associated increased risk for CVD. M e t h o d s and Results: The study population comprised 158 patients, 389 normolipidemic relatives and 90 spouses. FCH diagnosis was based on apolipoprotein B, triglyceride and total cholesterol levels. Adiponectin levels were determined using a commercially available ELISA. For both males and females, the mean serum adiponectin level (ttg/ml) was significantly lower in FCH patients (2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively) compared to normolipidemic relatives (2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively), and spouses (2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively). These differences remained after standardization of the adiponectin levels for BMI and insulin resistance. A decrease in serum adiponectin levels was associated with a more atherogenic lipid profile and insulin resistance, but not with an increased risk for CVD. Conclusions: Low adiponectin levels contribute to the FCH phenotype and may thus reflect a defect in adipose tissue metabolism in the pathophysiology of FCH.
W08-O-0031 A D I P O N E C T I N AND ITS ASSOCIATION W I T H M E T A B O L I C SYNDROME, INFLAMMATORY M A R K E R S AND DYSLIPIDEMIC PHENOTYPES H. Vaverkov~i 1, D. Novotn3~2, D. Kar~ek 1, D. Jackuliakovii 1 , M. Halenka 1, M. Budikovh 3 . 13rd Department of Internal Medicine,
Medical Faculty of Palacloj University Olomouc, Czech Republic; 2Department of Consolidated Laboratories, University Hospital Olomouc, Czech Republic; SDepartment of Nuclear Medicine, University Hospital Olomouc, Czech Republic Objective: Adiponectin is a recently discovered adipocytokine, which seems to be involved in insulin resistance, inflammation and atherosclerosis. The aim of the present study was to evaluate serum concentrations
75th EAS Congress, 23-26 April 2005, Prague, Czech Republic
0 I 0 03
HDL-C (mmol/I) 0.96+0.23 1.594- 0.47
LDL-C ApoA 1 (retool/I) (rag/all) 3.024-0.86 1124-13.9 2.81 4- 0.90 148 4- 23.5
ApoB (mg/dl) 103.84-25.5 86.6 4- 27.0
Conclusions: Smaller and potentially less protective HDL particles predominate in the fasting serum of the affected low HDL family members.
W8
V I S C E R A L FAT, A D I P O C Y T O K I N E S A N D C A R D I O V A S C U L A R RISK
W08-1S-001 J ADIPONECTIN AND THE M E T A B O L I C SYNDROME S.M. Brichard. Unit of Endocrinology and Metabolism, Faculty of Medicine, University of Louvain, UCL 5530, 55 Avenue Hippocrate, B-1200 Brussels, Belgium Adipose tissue secretes a large number of physiologically active peptides that often share structural properties with adipocytokiues, and are therefore referred to as adipocytokiues. Two adipecytokiues, leptin and adiponectin (ApN) exert major metabolic properties in mice. Their altered circulating profile may play a determinant role in the pathogenesis of human obesity and its related metabolic disorders (metabolic syndrome). ApN seems to he the most promising therapeutic target. This 247 aminoacid peptide is composed of an N-terminal collagenous domain and a C-terminal globular domain. In addition to full-length protein, the globular fragment (gApN), generated by proteolysis, may exhibit some activity. Full-length or proteolytic fragments of ApN exert hypolipemic, anti-diabetic, and perhaps anti-obesity properties (at least when energy intake is controlled) in mice. ApN also prevents the development of atherosclerosis and displays anti-inflammatory effects. Two types of adiponectin receptors are thought to mediate the metabolic effects of the hormone via stimulation of AMPK, PPARalpha and p38 MAPK. AdipoR1, which is a high-affinity receptor for gApN, is most abundantly expressed in skeletal muscle, while adipoR2, which serves as a moderute-affinity receptor for both forms of ApN, is predominant in liver. Circulating levels of ApN are paradoxically decreased in obesity and the metabolic syndrome. These low levels may have potential repercussions in the pathophysiology of this syndrome. This deficiency also raises the opportunity of a potential therapeutic supplementation. /
W08-1S-002 | THE ADIPOSE TISSUE AS AN ENDOCRINE ORGAN: IMPLICATION IN I N F L A M M A T I O N AND ATHEROSCLEROSIS M. Guerre-Millo. U465 INSERM, Paris France White adipose tissue 0NAT) produces a variety of bioactive peptides acting locally (autocrine/paracrine) or released into the blood stream to reach distant targets (endocrine). Alteration of WAT mass in obesity or lipoatrophy affects the production of most adipose secreted factors (termed "adipokines"). Since both conditions are associated with multiple metabolic disorders and increased risk of cardiovascular diseases, the idea has emerged that WAT could be instrumental in these complications by virtue of its secreted factors. Several adipokiues are increased in the obese state and have been implicated in obesity-linked hypertension (angiotensinogen), impaired fibrinolysis (PAl-I) and insulin resistance ('I'NFc~, IL-6, resistin). Leptin and adiponectin both exert an insalin-sensitizing effect, at least in part by favoring tissue fatty-acid oxidation through activation of AMP-activated kinase (AMPK). In obesity, leptin resistance coupled with decreased plasma adiponectin favor insulin resistance. Beside their common insulin-sensitizing effect, leptiu and adiponectin have distinct properties, leptin, as a long-term integrative signal of energy store and adiponectin, as a potent anti-atherogenic agent. Thus, through its secretory function, WAT lies at the heart of a complex network of factors capable of influencing several physiological processes. The possibility now exists to develop drugs targeting adipose secreted factors, representing a new approach to sensitize peripheral tissues to insulin and protect patients from atherosclerosis.
29
W08-O-001 ] FAMILIAL H Y P E R C H O L E S T E R O L E M I A PATIENTS W I T H CORONARY ARTERY DISEASE T. Bouhali 1, D. Brisson 1, G. Tremblay 1, C. Gagne 2, P. Couture 2, M.N. Vissers 3, B.A. Hutten 3, J.J. Kastelein 3, D. Gaudet I . 1Lipid Clinic
and CMGC, Chicoutimi Hospital, Chicoutimi, Canada, 2 CRMI~ Laval University Hospital, Quebec, Canada, 3 Depts. of Vascular Medicine and Clinical Epidemiology-Biostatistics, U. of Amsterdam, the Netherlands Familial hypercholesterolemia (FH) represents a major susceptibility phenotype for premature coronary artery disease (CAD) that frequently occurs in subjects under fifty. However, some FH eider subjects never developed CAD, even without treatment or appropriate diet. HDL-Cholesterol levels have been previously associated with a modulation of CAD risk in FH. The strong correlation between plasma HDL-Cholesterol and adiponectin levels, and the anti-inflammatory anti-atherogenic properties of the latter, suggest that adiponectin could also he involved in CAD risk modulation among FH. Objective: To examine the relationship between plasma adiponectin levels and age at the first CAD event in FH patients. Methods: Adiponectin concentrations were measured by Elisa, in a sample of 172 heterozygous French Canadian FH patients. Proportional hazard model and the tertiles of adiponectin levels were used. Results: Increased plasma adiponectin concentrations were associated with longer survival without CAD, independently of other covariates and even after an adjustment for HDL-Cholesterol (p = 0.004). Conclusion: Plasma adiponectin levels are associated with a reduction of premature CAD risk in FI-I, independently of known CAD risk modulators. The present results reinforce the idea that adiponectin could he a new promising therapeutic target in CAD prevention.
W08-O-002 ] DECREASED A D I P O N E C T I N LEVELS IN PATIENTS W I T H FAMILIAL COMBINED HYPERLIPIDEMIA G.M. van der Vleuteu L.J.H. van Tits, M. den Heijer, H.L.M. Hak-Lemmers, A.F.H. Stalenhoef, J. de Graaf. General Internal
Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Objective: Familial combined hypedipidemia (FCH) is characterized by hypercholesterolemia and/or hypeariglyceridemia and premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Adiponectiu is a secretory product of the adipose tissue. Low levels of adiponectin contribute to insulin resistance and are associated with accelerated atherogenesis. The aim of this study is to determine whether decreased adiponectin levels contribute to the FCH phenotype and its associated increased risk for CVD. M e t h o d s and Results: The study population comprised 158 patients, 389 normolipidemic relatives and 90 spouses. FCH diagnosis was based on apolipoprotein B, triglyceride and total cholesterol levels. Adiponectin levels were determined using a commercially available ELISA. For both males and females, the mean serum adiponectin level (ttg/ml) was significantly lower in FCH patients (2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively) compared to normolipidemic relatives (2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively), and spouses (2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively). These differences remained after standardization of the adiponectin levels for BMI and insulin resistance. A decrease in serum adiponectin levels was associated with a more atherogenic lipid profile and insulin resistance, but not with an increased risk for CVD. Conclusions: Low adiponectin levels contribute to the FCH phenotype and may thus reflect a defect in adipose tissue metabolism in the pathophysiology of FCH.
W08-O-0031 A D I P O N E C T I N AND ITS ASSOCIATION W I T H M E T A B O L I C SYNDROME, INFLAMMATORY M A R K E R S AND DYSLIPIDEMIC PHENOTYPES H. Vaverkov~i 1, D. Novotn3~2, D. Kar~ek 1, D. Jackuliakovii 1 , M. Halenka 1, M. Budikovh 3 . 13rd Department of Internal Medicine,
Medical Faculty of Palacloj University Olomouc, Czech Republic; 2Department of Consolidated Laboratories, University Hospital Olomouc, Czech Republic; SDepartment of Nuclear Medicine, University Hospital Olomouc, Czech Republic Objective: Adiponectin is a recently discovered adipocytokine, which seems to be involved in insulin resistance, inflammation and atherosclerosis. The aim of the present study was to evaluate serum concentrations
75th EAS Congress, 23-26 April 2005, Prague, Czech Republic
0 I 0 03