- Email: [email protected]
Human adipose tissue accumulation is connected with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue
e72
Abstracts / Atherosclerosis 263 (2017) e29ee110
activity in order to fulfill energy needs during cold exposure, discrepancies that point towards an extreme effort to maintain normal body temperature.
SAG117. HUMAN ADIPOSE TISSUE ACCUMULATION IS CONNECTED WITH PROINFLAMMATORY CHANGES IN SUBCUTANEOUS RATHER THAN VISCERAL ADIPOSE TISSUE Ivana Kralova Lesna1, Anna Kralova1, Sona Cejkova1, Jiri Fronek2, Marek Petras3, Filip Thieme2, Libor Janousek2, Rudolf Poledne1. 1 Insitute for Clinical and Experimental Medicine, Centre of Experimental Medicine, Lab.for Atherosclerosis Research, Prague, Czech Republic; 2 Institute for Clinical and Experimental Medicine, Transplant Surgery Dept, Prague, Czech Republic; 3 2nd Faculty of Medicine, Charles University, Prague, Czech Republic Aim: The importance of the involvement of adipose tissue macrophage subpopulations in obesity-related disorders is well known from different animal models, but human data are scarcer. Methods: Subcutaneous, visceral, and perivascular adipose tissue of 52 healthy living kidney donors were obtained during living donor nephrectomy. Stromal vascular fractions were isolated and analyzed by flow cytometry using CD14, CD16, CD36, and CD163 antibodies. Results: Total macrophage numbers in subcutaneous adipose tissue increased (p¼0.02) with body mass index (BMI), with a similar increase seen in the proportion of phagocytic CD14+CD16+CD36high macrophages (p<0.01). On the other hand, there was an inverse correlation between anti-inflammatory CD14+CD16-CD163+ macrophages (p<0.05) and BMI. These correlations disappeared after excluding obese subjects (BMI>30 kg/ m2) from the analysis. These relationships were also observed when the relationships of these macrophage subpopulations to waist circumference in this adipose tissue were analyzed. Interestingly, no such relations were found in visceral or perivascular adipose tissue. Conclusions: Obesity in subjects without metabolic syndrome is associated with distinct, highly phagocytic macrophage accumulation in subcutaneous adipose tissue. Interestingly, this effect was not observed in both visceral adipose tissues analyzed. Acknowledgements: This project was supported the project (Ministry of Health, Czech Republic) for development of research organization 00023001 (Institute for Clinical and Experimental Medicine, Prague, Czech Republic) e institutional support.
SAG118. CHANGES IN ADIPOSE TISSUE TRANSCRIPTOME OF APOE3L.CETP MICE DURING THE DEVELOPMENT OF THE METABOLIC SYNDROME Dimitris Nasias, Dimitris Kardassis. Laboratory of Biochemistry, University of Crete Medical School and IMBB-FORTH, Heraklion, Greece Aim: The metabolic syndrome (MetS) is a combination of disorders including obesity, insulin resistance, high plasma triglycerides/low HDL cholesterol and high blood pressure that render individuals at increased risk of developing cardiovascular diseases. The aim of this study was to monitor changes in the transcriptome of the white adipose tissue of apoE3L.CETP mice used as a model of MetS. Methods: ApoE3L.CETP male mice were fed high fat + cholesterol (HFD) or a low-fat diet (LFD) for different time periods. MetS development was assessed on the basis of body weight, total plasma cholesterol and triglycerides and OGTT. Adipose RNA was analyzed on Affymetrix Mouse Gene 2.0 ST arrays followed by bioinformatical analysis. Results: Microarray analysis revealed an increasing number of differentially expressed adipose transcripts during MetS development. In mice with full MetS (12 weeks in HFD), 1.222 transcripts were differentially expressed the majority of which (800 transcripts) were up-regulated. Pathway analysis revealed that the differentially expressed transcripts were clustered in networks associated with inflammatory/immunological responses and also in cell growth/proliferation and metabolic diseases
indicative of enhanced adipose tissue inflammation and metabolic dysfunction. The top list of pathways includes focal adhesion, chemokine, B and T cell receptor and MAPK signaling pathways. PPARa as well as PPAR gamma coactivators 1a and and 1b were down-regulated in MetS. Conclusions: The new MetS adipose signatures identified could be exploited further for the validation and the characterization of the role of specific adipose genes in MetS development and for diagnostic or therapeutic purposes.
SAG119. SERUM OXLDL-B2GPI COMPLEX VISCERAL ADIPOSE TISSUE
REFLECTS
INFLAMMATION
IN
Michaela Siklova1, Michal Koc1, Lenka Rossmeislova1, Pavel Kraml2. 1 Third Faculty of Medicine, Charles University, Department of Sport Medicine, Prague, Czech Republic; 2 University Hospital Kralovske Vinohrady, Second Department of Internal Medicine, Prague, Czech Republic Aim: Aim: OxLDL-ß2GPI complex has been suggested to play a role in the development of chronic inflammatory and metabolic disturbances associated with obesity, including insulin resistance, diabetes, and atherosclerosis. The aim of this study was to investigate the relationship between circulating oxLDL- ß2GPI and inflammatory state in the subcutaneous and visceral adipose tissue. Methods: Methods: Cohort of 36 women with wide range of BMI (17-48 kg/m2) and metabolic status (with or without metabolic syndrome (MS) was investigated. Serum levels of oxLDL-ß2GPI were measured by ELISA, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. mRNA expression of several macrophage markers was determined in subcutaneous and visceral adipose tissue by qPCR. Results: Results: Serum oxLDL-ß2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17 ± 1.97, p < 0.001; vs obese without MS: 16.36 ± 2.89, p < 0.05). Serum oxLDL-ß2GPI also correlated with MS indices (HDL, TG, waist) and with mRNA expression of macrophage markers (namely FCGBP, MSR1, PLA2G7, ACP5, etc.) in visceral adipose tissue. Conclusions: Conclusion: We have shown in this study, that circulating oxLDL-ß2GPI reflects inflammatory status of visceral adipose tissue in obese subjects and correlates with metabolic syndrome indices. Thus, oxLDL-ß2GPI seems to be an important marker of adipose tissue inflammatory state and possibly a factor contributing to metabolic and cardiovascular complications associated with metabolic syndrome. Acknowledgement: The work was supported by grant GACR 16-14048S and by Projects PRVOUK P31 and UNCE 20431 from Charles University in Prague
SAG120. EPICARDIAL FAT VOLUME IN WOMEN WITH CHEST PAIN AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE e THE IPOWER STUDY Persia Shahriari1, D. Frestad1, 2, M.M. Michelsen1, N.D. Mygind1, 3, A. Pena1, 4, J.D. Hove2, I. Gustafsson2, E. Prescott1. 1 Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; 2 Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; 3 Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 4 Department of Cardiology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark Aim: Women with angina pectoris and angiographically normal coronary arteries are at increased cardiovascular (CV) risk. Epicardial fat (EF), an active producer of inflammatory factors, is situated in close relation to the adventitia of the coronary arteries and is associated with development of CAD and adverse prognosis. The aim of this study is to assess the EF volume using Multi Detector Computed Tomography (MDCT) in women with angina and no obstructive coronary artery disease (CAD) and asymptomatic controls.
Abstracts / Atherosclerosis 263 (2017) e29ee110
activity in order to fulfill energy needs during cold exposure, discrepancies that point towards an extreme effort to maintain normal body temperature.
SAG117. HUMAN ADIPOSE TISSUE ACCUMULATION IS CONNECTED WITH PROINFLAMMATORY CHANGES IN SUBCUTANEOUS RATHER THAN VISCERAL ADIPOSE TISSUE Ivana Kralova Lesna1, Anna Kralova1, Sona Cejkova1, Jiri Fronek2, Marek Petras3, Filip Thieme2, Libor Janousek2, Rudolf Poledne1. 1 Insitute for Clinical and Experimental Medicine, Centre of Experimental Medicine, Lab.for Atherosclerosis Research, Prague, Czech Republic; 2 Institute for Clinical and Experimental Medicine, Transplant Surgery Dept, Prague, Czech Republic; 3 2nd Faculty of Medicine, Charles University, Prague, Czech Republic Aim: The importance of the involvement of adipose tissue macrophage subpopulations in obesity-related disorders is well known from different animal models, but human data are scarcer. Methods: Subcutaneous, visceral, and perivascular adipose tissue of 52 healthy living kidney donors were obtained during living donor nephrectomy. Stromal vascular fractions were isolated and analyzed by flow cytometry using CD14, CD16, CD36, and CD163 antibodies. Results: Total macrophage numbers in subcutaneous adipose tissue increased (p¼0.02) with body mass index (BMI), with a similar increase seen in the proportion of phagocytic CD14+CD16+CD36high macrophages (p<0.01). On the other hand, there was an inverse correlation between anti-inflammatory CD14+CD16-CD163+ macrophages (p<0.05) and BMI. These correlations disappeared after excluding obese subjects (BMI>30 kg/ m2) from the analysis. These relationships were also observed when the relationships of these macrophage subpopulations to waist circumference in this adipose tissue were analyzed. Interestingly, no such relations were found in visceral or perivascular adipose tissue. Conclusions: Obesity in subjects without metabolic syndrome is associated with distinct, highly phagocytic macrophage accumulation in subcutaneous adipose tissue. Interestingly, this effect was not observed in both visceral adipose tissues analyzed. Acknowledgements: This project was supported the project (Ministry of Health, Czech Republic) for development of research organization 00023001 (Institute for Clinical and Experimental Medicine, Prague, Czech Republic) e institutional support.
SAG118. CHANGES IN ADIPOSE TISSUE TRANSCRIPTOME OF APOE3L.CETP MICE DURING THE DEVELOPMENT OF THE METABOLIC SYNDROME Dimitris Nasias, Dimitris Kardassis. Laboratory of Biochemistry, University of Crete Medical School and IMBB-FORTH, Heraklion, Greece Aim: The metabolic syndrome (MetS) is a combination of disorders including obesity, insulin resistance, high plasma triglycerides/low HDL cholesterol and high blood pressure that render individuals at increased risk of developing cardiovascular diseases. The aim of this study was to monitor changes in the transcriptome of the white adipose tissue of apoE3L.CETP mice used as a model of MetS. Methods: ApoE3L.CETP male mice were fed high fat + cholesterol (HFD) or a low-fat diet (LFD) for different time periods. MetS development was assessed on the basis of body weight, total plasma cholesterol and triglycerides and OGTT. Adipose RNA was analyzed on Affymetrix Mouse Gene 2.0 ST arrays followed by bioinformatical analysis. Results: Microarray analysis revealed an increasing number of differentially expressed adipose transcripts during MetS development. In mice with full MetS (12 weeks in HFD), 1.222 transcripts were differentially expressed the majority of which (800 transcripts) were up-regulated. Pathway analysis revealed that the differentially expressed transcripts were clustered in networks associated with inflammatory/immunological responses and also in cell growth/proliferation and metabolic diseases
indicative of enhanced adipose tissue inflammation and metabolic dysfunction. The top list of pathways includes focal adhesion, chemokine, B and T cell receptor and MAPK signaling pathways. PPARa as well as PPAR gamma coactivators 1a and and 1b were down-regulated in MetS. Conclusions: The new MetS adipose signatures identified could be exploited further for the validation and the characterization of the role of specific adipose genes in MetS development and for diagnostic or therapeutic purposes.
SAG119. SERUM OXLDL-B2GPI COMPLEX VISCERAL ADIPOSE TISSUE
REFLECTS
INFLAMMATION
IN
Michaela Siklova1, Michal Koc1, Lenka Rossmeislova1, Pavel Kraml2. 1 Third Faculty of Medicine, Charles University, Department of Sport Medicine, Prague, Czech Republic; 2 University Hospital Kralovske Vinohrady, Second Department of Internal Medicine, Prague, Czech Republic Aim: Aim: OxLDL-ß2GPI complex has been suggested to play a role in the development of chronic inflammatory and metabolic disturbances associated with obesity, including insulin resistance, diabetes, and atherosclerosis. The aim of this study was to investigate the relationship between circulating oxLDL- ß2GPI and inflammatory state in the subcutaneous and visceral adipose tissue. Methods: Methods: Cohort of 36 women with wide range of BMI (17-48 kg/m2) and metabolic status (with or without metabolic syndrome (MS) was investigated. Serum levels of oxLDL-ß2GPI were measured by ELISA, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. mRNA expression of several macrophage markers was determined in subcutaneous and visceral adipose tissue by qPCR. Results: Results: Serum oxLDL-ß2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17 ± 1.97, p < 0.001; vs obese without MS: 16.36 ± 2.89, p < 0.05). Serum oxLDL-ß2GPI also correlated with MS indices (HDL, TG, waist) and with mRNA expression of macrophage markers (namely FCGBP, MSR1, PLA2G7, ACP5, etc.) in visceral adipose tissue. Conclusions: Conclusion: We have shown in this study, that circulating oxLDL-ß2GPI reflects inflammatory status of visceral adipose tissue in obese subjects and correlates with metabolic syndrome indices. Thus, oxLDL-ß2GPI seems to be an important marker of adipose tissue inflammatory state and possibly a factor contributing to metabolic and cardiovascular complications associated with metabolic syndrome. Acknowledgement: The work was supported by grant GACR 16-14048S and by Projects PRVOUK P31 and UNCE 20431 from Charles University in Prague
SAG120. EPICARDIAL FAT VOLUME IN WOMEN WITH CHEST PAIN AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE e THE IPOWER STUDY Persia Shahriari1, D. Frestad1, 2, M.M. Michelsen1, N.D. Mygind1, 3, A. Pena1, 4, J.D. Hove2, I. Gustafsson2, E. Prescott1. 1 Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; 2 Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; 3 Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 4 Department of Cardiology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark Aim: Women with angina pectoris and angiographically normal coronary arteries are at increased cardiovascular (CV) risk. Epicardial fat (EF), an active producer of inflammatory factors, is situated in close relation to the adventitia of the coronary arteries and is associated with development of CAD and adverse prognosis. The aim of this study is to assess the EF volume using Multi Detector Computed Tomography (MDCT) in women with angina and no obstructive coronary artery disease (CAD) and asymptomatic controls.