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Abstracts / Atherosclerosis 252 (2016) e1ee196
Intermediary Metabolism, Cantanhede, Portugal; 4 Univ. of Copenhagen, Dep. of Biology, Copenhagen, Denmark Objectives: 1)Combined intervention using n-3 polyunsaturated fatty acids (n-3 PUFA) and calorie restriction (CR) in dietary obese B57BL6/J (B6/J)mice and 2)cold exposure using obesity- and atherosclerosis-resistant A/J and obesity- and atherosclerosis-prone (B6/J) chow-fed mice were chosen to study metabolic changes in WAT. Its metabolic activity is relatively low, however several pieces of evidence indicate that UCP1-independen activation of futile TG/FA cycle in adipocytes could influence total energy balance and could prevent obesity and obesity releated chronic inflammation. Methods: The activity of futile TG/FA cycle was measured by 2H-NMR. qPCR was used to find out, if genes involved in mitochondrial biogenesis, FA oxidation and glyceroneogenesis were changed. Results: 1)The combined intervention (n-3 PUFA + CR) had the anti-inflammatory effect. PPARg signaling was activated in response to formation of lipid mediators such as 15d-PGJ2. 2) A decrease in depot weight was observed in cold exposed animals in both subcutaneous and epididymal WAT, the effect was more pronounced in the case of A/J mice. TG/FA cycle was elevated, again more in A/J. In both experiments genes involved in mitochondrial biogenesis, FA oxidation and glyceroneogenesis were increased. Conclusions: Our results support the view that high capacity of mitochondrial OXPHOS linked to inducible TAG/FA cycling activity is essential for metabolic flexibility of WAT, may support leanness, lower chronic tissue inflammation and be helpful for not increasing TAG and NEFA in system circulation, which can contribute to the formation of atherosclerotic plaques. Supported by the Czech Science Foundation (16-05151S)
EAS16-0984, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. RELATIONSHIP OF ORPHAN RECEPTOR RORa AND CHOLESTEROL TRANSPORTERS ABCA1 AND ABCG1 EXPRESSION IN VISCERAL ADIPOSE TISSUE V. Miroshnikova 1, A. Panteleeva 1, E. Demina 1, T. Usenko 1, E. Bazhenova 2, I. Semenova 1, O. Berkovich 2, E. Baranova 2, S. Pchelina 1. 1 B.P. Kontantinov Petersburg Nuclear Physics Institute, Molecular and Radiation Biophysics, Gatchina, Russia; 2 Pavlov State Medical University, Cardiology, Saint-Petersburg, Russia Objectives: RAR-related orphan receptor RORa is a nuclear receptor involved in the circadian system, lipid metabolism and regulation of adipogenesis. While adiposity is associated with impaired lipid homeostasis and cholesterol accumulation in adipose tissue, ATP-binding cassette transporters ABCA1 and ABCG1 play a major role in cellular cholesterol efflux in adipocytes. We investigated whether regulation of adipocyte ABCA1 and ABCG1 might also be a target pathway of RORa and play a role in human obesity. The aim of this study was to investigate correlation between orphan receptor RORa and ABCA1 and ABCG1 transporters in intraabdominal adipose tissue. Methods: Visceral fat was received from gastrocolic omentum during laparoscopic cholecystectomy from 37 individuals: obese/overweight (BMI25; N¼23) and normal weight (BMI<25; N¼14). ABCA1, ABCG1 and RORa mRNA levels were determined by Real-Time PCR. Protein levels were measured by Western-blot. Results: RORa mRNA level was reduced in the obese/overweight group compared with the normal weight group (p<0.02). A positive correlation between RORa and ABCA1 (r¼0.48; p<0.05) and ABCG1 (r¼0.43; p<0.05) protein levels in visceral fat was shown. An interesting discrepancy between ABCA1 and ABCG1 mRNA and protein levels was demonstrated. ABCA1 and ABCG1 protein levels were higher in overweight individuals compared with normal weight (p<0.01; p<0.05), this was not observed for morbidly obese individuals despite of ABCA1 and ABCG1 mRNA levels were positively correlated with BMI.
Conclusions: Our results suggest RORa may control ABCA1 and ABCG1 protein levels in visceral fat tissue and thus influence on the obesity development. The research was supported by RFFR 14-04-31690 grant.
EAS16-0234, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. EPICARDIAL FAT AND BMI RELATIONSHIPS WITH CORONARY ATHEROSCLEROTIC MARKERS IN PATIENTS WITH CORONARY CALCIUM SCORE >0: THE EFFECT OF AGE AND GENDER A. Albasri 1, H. Nafakhi 2, A. Almusawi 3, H. Alnafakh 3. 1 Alsader Teaching hospital, Cardiac Center, Najaf, Iraq; 2 University of Kufa, Internal Medicine, Kufa, Iraq; 3 University of Kufa, Radiology, Kufa, Iraq Objectives: To study the effect of age and gender on the relationship of obesity measures(EFV and BMI) with coronary atherosclerotic markers (croaonry calcificed plaque(CCP) and coronary artery obstructive disease (CAD)) in patients with coronary calcium score >0(CAC). Methods: From a total 339 consecutive patients with suspected coronary disease, 145 patients with CAC >0 measured according to the Agatston method were eligible to enroll in this study. EFV was defined as any fatty tissue located within the pericardial sac. CAD was visually graded as nonsignificant stenosis with a mean lumen diameter reduction of < 50 % or significant stenosis with a mean lumen diameter reduction of 50 % in a single vessel. Results: Patients aged 50 years: Consisted of 31 patients. No significant correlations were observed between EFV with CAD and CCP while BMI showed a significant correlation with CCP only (P¼0.01). Patients aged > 50 years: consisted of 114 patients.EFV was significantly correlated with CAD (P¼0.01). No significant correlations were observed between EFV with CCP. BMI showed no significant correlations with CAD and CCP. Male patients: Consisted of 85 patients .EFV was significantly correlated with CAD(P¼0.007) while BMI showed no significant correlation with CAD. No significant correlations were observed between EFV and BMI with CCP. Female patients: Consisted of 60 patients. No significant correlations were observed between EFV and BMI with CAD and CCP. Conclusions: In patients with CAC >0, BMI showed significant correlation with coronary atherosclerosis in young patients while EFV was significantly correlated with coronary atherosclerotic markers in male patients aged > 50 years.
EAS16-0624, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. COLD-INDUCED CHANGES IN WHITE ADIPOSE TISSUE OF A/J AND C57BL/6J MICE K. Bardova, P. Flachs, K. Adamcova, M. Svobodova, J. Kopecky. Institute of Physiology of the Czech Academy of Sciences, Department of Adipose Tissue Biology, Prague 4, Czech Republic Objectives: During short-term cold exposure, thermogenesis and energy consumption is increased and energy stores are partially depleted. The ability to withdraw lipids from adipose tissue is to some extend dependent on a sufficient vascular network and a presence of adipocytes with high lipolytical and re-esterification rate. Thus, we attempted to define the impact of cold on epididymal white adipose tissue (eWAT) of atherosclerosis- and obesity-resistant A/J and prone C57BL/6J mice. Methods: A/J and C57BL/6J 3-month-old male mice fed standard chow were maintained at thermoneutral temperature (30 C), or exposed to cold (6 C for 48 hours) before dissection. ATGL, DGAT1 and isolectin IB4 were immunohistochemically detected. mRNAs for Atgl and Dgat1 were evaluated using quantitative RT-PCR. Results: Cold exposure in eWAT leads to a decrease in depot weight; the effect is more pronounced in the case of A/J mice and may be connected to
Abstracts / Atherosclerosis 252 (2016) e1ee196
e131
generally higher vascularisation around unilocular cells and higher increase of vascular network after cold exposure in A/J mice. Cold induces emergence of UCP1-negative and ATGL- and DGAT1-positive cells more in A/J mice, as confirmed by induction of Atgl and Dgat1 mRNA. Conclusions: In response to cold, paucilocular cells and vascular network are induced in eWAT and this effect is more pronounced in A/J mice. Paucilocular cells are ATGL- and DGAT1-possitive, indicating higher lipolysis and re-esterification in A/J as compared to C57BL/6J mice. Supported by the Czech Science Foundation (16-05151S)
University Hospital Heidelberg, Institute for Diabetes and Cancer IDC, Neuherberg, Germany
EAS16-0578, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. RELATION BETWEEN EPICARDIAL FAT TISSUE AND INFLAMMATORY MARKERS IN PREGNANTS WITH PREECLAMPSIA
Methods: Various cationic liposomes with different composition, size and surface properties were tested and loaded with miR-26a. Particle size, surface charge, entrapment efficiency and stability were determined by dynamic light scattering, zeta potential and native PAGE. Efficiency of the formulations was evaluated in comparison to commercially available transfection reagents by measuring the miR-26a-induced upregulation of the key thermogenic marker uncoupling protein 1 (UCP1) in human adipocytes. Results: Specific liposome compositions (e.g. DOPE/DOTAP/DC-Cholesterol ¼ 45/49/6 %molar ratio), which show adequate miR-26a loading efficiencies (lipid:miR-26a molar ratio of 200:1), resistance to nuclease degradation and tolerable cell toxicity were identified. The size of the liposomes was adjusted by size extrusion to about 140 nm with a polydispersity index below 0.1. Relative UCP1 expression levels were determined by RT-qPCR. The values for liposomes were comparable or even higher than those achieved with conventional HiPerFect transfection reagent (positive control). Conclusions: We succeeded in the identification of liposomes for efficient delivery of functional small RNAs into human adipocytes. Such formulations can be functionalized for targeting adipocytes to be tested in vivo in a mouse model of obesity.
H.A. Cakmak 1, B. Dincgez Cakmak 2, C. Yayla Abide 3, E. Inci Coskun 4, M. Erturk 5. 1 Mustafakemalpasa State Hospital, Cardiology, Bursa, Turkey; 2 Bursa Sevket Yilmaz Training and Research Hospital, Obstetric and Gynecology, Bursa, Turkey; 3 Zeynep Kamil Maternity and Children Training and Research Hospital, Obstetric and Gynecology, Istanbul, Turkey; 4 Inonu University-School of Medicine, Obstetric and Gynecology, Malatya, Turkey; 5 Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Cardiology, Istanbul, Turkey Objectives: Epicardial fat tissue (EFT) releases a variety of proinflammatory cytokines which play crucial roles in the development of several cardiovascular diseases such as chronic hypertension and atherosclerosis. Preeclampsia, which is a major cause of maternal mortality and morbidity, is related to severe chronic inflammation, endothelial dysfunction and oxidative stress. Pentraxin-3 (PTX-3) and neutrophil to lymhocyte ratio (NLR) have been proposed as a new marker of systemic inflammation in recent studies. Since, there is a few information about the relationship between EFT, PTX3 and NLR in preeclampsia, the aim of the present study was to investigate this association in this setting. Methods: A total of 100 pregnant subjects with the diagnosis of preeclampsia were recruited as a preeclamptic group. Control group included of 40 subjects, who had no known hypertension, and an uncomplicated pregnancy, presented to the obstetrics and gynecology outpatient clinic for routine prenatal screenings. PTX-3 levels were measured with the enzyme-linked immunosorbent assay (ELISA) method and NLR was calculated as the ratio of the neutrophils and lymphocytes both obtained from blood sample at admission. Results: PTX-3 (3.9±3.5 vs. 1.5±0.8 ng/ml,p<0.001) and NLR (5.3±1.4 vs. 3.0±0.8,p<0.001) were significantly higher in the preeclampsia group than the normal pregnants. EFT was also found to be significantly higher in the preeclampsia group as compared to controls (6.8±0.7 vs. 5.9±0.7 mm,p<0.001). EFT was significantly correlated with both PTX-3 and NLR in preeclamptic pregnants (r¼0.307,p<0.001 and r¼0.448, p<0.001 respectively). Conclusions: EFT, which is an inexpensive and readily available echocardiographic marker, is associated with new inflammatory markers in preeclampsia.
EAS16-0277, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. LIPOSOMES FOR MICRORNA DELIVERY TO HUMAN ADIPOCYTES G. Schratter 1, M. Karbiener 2, G. Almer 3, H. Mangge 3, M. Scheideler 4, R. Prassl 1. 1 Medical University of Graz, Institute of Biophysics, Graz, Austria; 2 ENT University Hospital Medical University of Graz, Division of Phoniatrics, Graz, Austria; 3 Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria; 4 Helmholtz Center Munich and Joint Heidelberg-IDC Translational Diabetes Program
Objectives: Obesity and atherosclerosis-related diseases account for over one-third of deaths worldwide. A novel strategy to combat obesity is the recruitment of thermogenic adipocytes. Only recently, a microRNA (miR26a) was identified by our group as regulator of white and brite/beige adipocyte differentiation. However, to be applied as novel therapeutics, microRNAs need proper delivery systems to achieve efficient intracellular uptake.
EAS16-0571, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. OVARIECTOMY AFFECTS SUBSTRATE UTILIZATION IN BROWN ADIPOSE TISSUE AND INDUCES LIVER DICARBONYL STRESS IN RATS J. Trnovska, H. Malinska, V. Skop, L. Kazdova. Institute for Clinical and Experimental Medicine, Center for Experimental medicine, Prague, Czech Republic Objectives: Postmenopausal metabolic syndrome may leads to increase in body weight, visceral obesity, insulin resistance, fatty liver and type 2 diabetes. Important player in substrate utilization is brown adipose tissue (BAT). BAT takes up and dissipates energy substrates that are present in excess in metabolic syndrome. We investigated the effects of ovariectomy (OVX) on the substrate utilization in BAT and white adipose tissue (WAT) and liver carbonyl and oxidative stress. Methods: OVX and shame-operated female Wistar rats were fed a standard diet for 4 months after OVX. 14C-palmitic acid and 14C-U-glucose oxidation and incorporation into lipid, and lipolysis, were measured in the visceral WAT and interscapular BAT ex vivo. The concentrations of methylglyoxal and glutathione in the liver were determined using the HPLCmethod with fluorescence detection. Results: OVX rats gained weight +15% compared to controls. Insulin sensitivity of white visceral adipose and muscle tissue was significantly decreased (WAT: -83%;p<0.05 and muscle: 60%;p˂0.01) in OVX rats. Severe hepatic triglycerides accumulation (+57%;p<0.001) in OVX rats associated with significantly elevated level of methylglyoxal (+57%;p˂0.01) may have contributed to the development of liver steatosis. Ovariectomy led to impaired balance GSH/GSSG (15.4±1.3vs.28.4±1.4;p˂0.01). BAT of OVX rats exhibited a reduced fatty acid oxidation (-137%;p<0.05), lipogenesis (-36%;p<0.05) and decreased lipolysis (-36%;p<0.05).
Abstracts / Atherosclerosis 252 (2016) e1ee196
Intermediary Metabolism, Cantanhede, Portugal; 4 Univ. of Copenhagen, Dep. of Biology, Copenhagen, Denmark Objectives: 1)Combined intervention using n-3 polyunsaturated fatty acids (n-3 PUFA) and calorie restriction (CR) in dietary obese B57BL6/J (B6/J)mice and 2)cold exposure using obesity- and atherosclerosis-resistant A/J and obesity- and atherosclerosis-prone (B6/J) chow-fed mice were chosen to study metabolic changes in WAT. Its metabolic activity is relatively low, however several pieces of evidence indicate that UCP1-independen activation of futile TG/FA cycle in adipocytes could influence total energy balance and could prevent obesity and obesity releated chronic inflammation. Methods: The activity of futile TG/FA cycle was measured by 2H-NMR. qPCR was used to find out, if genes involved in mitochondrial biogenesis, FA oxidation and glyceroneogenesis were changed. Results: 1)The combined intervention (n-3 PUFA + CR) had the anti-inflammatory effect. PPARg signaling was activated in response to formation of lipid mediators such as 15d-PGJ2. 2) A decrease in depot weight was observed in cold exposed animals in both subcutaneous and epididymal WAT, the effect was more pronounced in the case of A/J mice. TG/FA cycle was elevated, again more in A/J. In both experiments genes involved in mitochondrial biogenesis, FA oxidation and glyceroneogenesis were increased. Conclusions: Our results support the view that high capacity of mitochondrial OXPHOS linked to inducible TAG/FA cycling activity is essential for metabolic flexibility of WAT, may support leanness, lower chronic tissue inflammation and be helpful for not increasing TAG and NEFA in system circulation, which can contribute to the formation of atherosclerotic plaques. Supported by the Czech Science Foundation (16-05151S)
EAS16-0984, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. RELATIONSHIP OF ORPHAN RECEPTOR RORa AND CHOLESTEROL TRANSPORTERS ABCA1 AND ABCG1 EXPRESSION IN VISCERAL ADIPOSE TISSUE V. Miroshnikova 1, A. Panteleeva 1, E. Demina 1, T. Usenko 1, E. Bazhenova 2, I. Semenova 1, O. Berkovich 2, E. Baranova 2, S. Pchelina 1. 1 B.P. Kontantinov Petersburg Nuclear Physics Institute, Molecular and Radiation Biophysics, Gatchina, Russia; 2 Pavlov State Medical University, Cardiology, Saint-Petersburg, Russia Objectives: RAR-related orphan receptor RORa is a nuclear receptor involved in the circadian system, lipid metabolism and regulation of adipogenesis. While adiposity is associated with impaired lipid homeostasis and cholesterol accumulation in adipose tissue, ATP-binding cassette transporters ABCA1 and ABCG1 play a major role in cellular cholesterol efflux in adipocytes. We investigated whether regulation of adipocyte ABCA1 and ABCG1 might also be a target pathway of RORa and play a role in human obesity. The aim of this study was to investigate correlation between orphan receptor RORa and ABCA1 and ABCG1 transporters in intraabdominal adipose tissue. Methods: Visceral fat was received from gastrocolic omentum during laparoscopic cholecystectomy from 37 individuals: obese/overweight (BMI25; N¼23) and normal weight (BMI<25; N¼14). ABCA1, ABCG1 and RORa mRNA levels were determined by Real-Time PCR. Protein levels were measured by Western-blot. Results: RORa mRNA level was reduced in the obese/overweight group compared with the normal weight group (p<0.02). A positive correlation between RORa and ABCA1 (r¼0.48; p<0.05) and ABCG1 (r¼0.43; p<0.05) protein levels in visceral fat was shown. An interesting discrepancy between ABCA1 and ABCG1 mRNA and protein levels was demonstrated. ABCA1 and ABCG1 protein levels were higher in overweight individuals compared with normal weight (p<0.01; p<0.05), this was not observed for morbidly obese individuals despite of ABCA1 and ABCG1 mRNA levels were positively correlated with BMI.
Conclusions: Our results suggest RORa may control ABCA1 and ABCG1 protein levels in visceral fat tissue and thus influence on the obesity development. The research was supported by RFFR 14-04-31690 grant.
EAS16-0234, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. EPICARDIAL FAT AND BMI RELATIONSHIPS WITH CORONARY ATHEROSCLEROTIC MARKERS IN PATIENTS WITH CORONARY CALCIUM SCORE >0: THE EFFECT OF AGE AND GENDER A. Albasri 1, H. Nafakhi 2, A. Almusawi 3, H. Alnafakh 3. 1 Alsader Teaching hospital, Cardiac Center, Najaf, Iraq; 2 University of Kufa, Internal Medicine, Kufa, Iraq; 3 University of Kufa, Radiology, Kufa, Iraq Objectives: To study the effect of age and gender on the relationship of obesity measures(EFV and BMI) with coronary atherosclerotic markers (croaonry calcificed plaque(CCP) and coronary artery obstructive disease (CAD)) in patients with coronary calcium score >0(CAC). Methods: From a total 339 consecutive patients with suspected coronary disease, 145 patients with CAC >0 measured according to the Agatston method were eligible to enroll in this study. EFV was defined as any fatty tissue located within the pericardial sac. CAD was visually graded as nonsignificant stenosis with a mean lumen diameter reduction of < 50 % or significant stenosis with a mean lumen diameter reduction of 50 % in a single vessel. Results: Patients aged 50 years: Consisted of 31 patients. No significant correlations were observed between EFV with CAD and CCP while BMI showed a significant correlation with CCP only (P¼0.01). Patients aged > 50 years: consisted of 114 patients.EFV was significantly correlated with CAD (P¼0.01). No significant correlations were observed between EFV with CCP. BMI showed no significant correlations with CAD and CCP. Male patients: Consisted of 85 patients .EFV was significantly correlated with CAD(P¼0.007) while BMI showed no significant correlation with CAD. No significant correlations were observed between EFV and BMI with CCP. Female patients: Consisted of 60 patients. No significant correlations were observed between EFV and BMI with CAD and CCP. Conclusions: In patients with CAC >0, BMI showed significant correlation with coronary atherosclerosis in young patients while EFV was significantly correlated with coronary atherosclerotic markers in male patients aged > 50 years.
EAS16-0624, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. COLD-INDUCED CHANGES IN WHITE ADIPOSE TISSUE OF A/J AND C57BL/6J MICE K. Bardova, P. Flachs, K. Adamcova, M. Svobodova, J. Kopecky. Institute of Physiology of the Czech Academy of Sciences, Department of Adipose Tissue Biology, Prague 4, Czech Republic Objectives: During short-term cold exposure, thermogenesis and energy consumption is increased and energy stores are partially depleted. The ability to withdraw lipids from adipose tissue is to some extend dependent on a sufficient vascular network and a presence of adipocytes with high lipolytical and re-esterification rate. Thus, we attempted to define the impact of cold on epididymal white adipose tissue (eWAT) of atherosclerosis- and obesity-resistant A/J and prone C57BL/6J mice. Methods: A/J and C57BL/6J 3-month-old male mice fed standard chow were maintained at thermoneutral temperature (30 C), or exposed to cold (6 C for 48 hours) before dissection. ATGL, DGAT1 and isolectin IB4 were immunohistochemically detected. mRNAs for Atgl and Dgat1 were evaluated using quantitative RT-PCR. Results: Cold exposure in eWAT leads to a decrease in depot weight; the effect is more pronounced in the case of A/J mice and may be connected to
Abstracts / Atherosclerosis 252 (2016) e1ee196
e131
generally higher vascularisation around unilocular cells and higher increase of vascular network after cold exposure in A/J mice. Cold induces emergence of UCP1-negative and ATGL- and DGAT1-positive cells more in A/J mice, as confirmed by induction of Atgl and Dgat1 mRNA. Conclusions: In response to cold, paucilocular cells and vascular network are induced in eWAT and this effect is more pronounced in A/J mice. Paucilocular cells are ATGL- and DGAT1-possitive, indicating higher lipolysis and re-esterification in A/J as compared to C57BL/6J mice. Supported by the Czech Science Foundation (16-05151S)
University Hospital Heidelberg, Institute for Diabetes and Cancer IDC, Neuherberg, Germany
EAS16-0578, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. RELATION BETWEEN EPICARDIAL FAT TISSUE AND INFLAMMATORY MARKERS IN PREGNANTS WITH PREECLAMPSIA
Methods: Various cationic liposomes with different composition, size and surface properties were tested and loaded with miR-26a. Particle size, surface charge, entrapment efficiency and stability were determined by dynamic light scattering, zeta potential and native PAGE. Efficiency of the formulations was evaluated in comparison to commercially available transfection reagents by measuring the miR-26a-induced upregulation of the key thermogenic marker uncoupling protein 1 (UCP1) in human adipocytes. Results: Specific liposome compositions (e.g. DOPE/DOTAP/DC-Cholesterol ¼ 45/49/6 %molar ratio), which show adequate miR-26a loading efficiencies (lipid:miR-26a molar ratio of 200:1), resistance to nuclease degradation and tolerable cell toxicity were identified. The size of the liposomes was adjusted by size extrusion to about 140 nm with a polydispersity index below 0.1. Relative UCP1 expression levels were determined by RT-qPCR. The values for liposomes were comparable or even higher than those achieved with conventional HiPerFect transfection reagent (positive control). Conclusions: We succeeded in the identification of liposomes for efficient delivery of functional small RNAs into human adipocytes. Such formulations can be functionalized for targeting adipocytes to be tested in vivo in a mouse model of obesity.
H.A. Cakmak 1, B. Dincgez Cakmak 2, C. Yayla Abide 3, E. Inci Coskun 4, M. Erturk 5. 1 Mustafakemalpasa State Hospital, Cardiology, Bursa, Turkey; 2 Bursa Sevket Yilmaz Training and Research Hospital, Obstetric and Gynecology, Bursa, Turkey; 3 Zeynep Kamil Maternity and Children Training and Research Hospital, Obstetric and Gynecology, Istanbul, Turkey; 4 Inonu University-School of Medicine, Obstetric and Gynecology, Malatya, Turkey; 5 Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Cardiology, Istanbul, Turkey Objectives: Epicardial fat tissue (EFT) releases a variety of proinflammatory cytokines which play crucial roles in the development of several cardiovascular diseases such as chronic hypertension and atherosclerosis. Preeclampsia, which is a major cause of maternal mortality and morbidity, is related to severe chronic inflammation, endothelial dysfunction and oxidative stress. Pentraxin-3 (PTX-3) and neutrophil to lymhocyte ratio (NLR) have been proposed as a new marker of systemic inflammation in recent studies. Since, there is a few information about the relationship between EFT, PTX3 and NLR in preeclampsia, the aim of the present study was to investigate this association in this setting. Methods: A total of 100 pregnant subjects with the diagnosis of preeclampsia were recruited as a preeclamptic group. Control group included of 40 subjects, who had no known hypertension, and an uncomplicated pregnancy, presented to the obstetrics and gynecology outpatient clinic for routine prenatal screenings. PTX-3 levels were measured with the enzyme-linked immunosorbent assay (ELISA) method and NLR was calculated as the ratio of the neutrophils and lymphocytes both obtained from blood sample at admission. Results: PTX-3 (3.9±3.5 vs. 1.5±0.8 ng/ml,p<0.001) and NLR (5.3±1.4 vs. 3.0±0.8,p<0.001) were significantly higher in the preeclampsia group than the normal pregnants. EFT was also found to be significantly higher in the preeclampsia group as compared to controls (6.8±0.7 vs. 5.9±0.7 mm,p<0.001). EFT was significantly correlated with both PTX-3 and NLR in preeclamptic pregnants (r¼0.307,p<0.001 and r¼0.448, p<0.001 respectively). Conclusions: EFT, which is an inexpensive and readily available echocardiographic marker, is associated with new inflammatory markers in preeclampsia.
EAS16-0277, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. LIPOSOMES FOR MICRORNA DELIVERY TO HUMAN ADIPOCYTES G. Schratter 1, M. Karbiener 2, G. Almer 3, H. Mangge 3, M. Scheideler 4, R. Prassl 1. 1 Medical University of Graz, Institute of Biophysics, Graz, Austria; 2 ENT University Hospital Medical University of Graz, Division of Phoniatrics, Graz, Austria; 3 Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria; 4 Helmholtz Center Munich and Joint Heidelberg-IDC Translational Diabetes Program
Objectives: Obesity and atherosclerosis-related diseases account for over one-third of deaths worldwide. A novel strategy to combat obesity is the recruitment of thermogenic adipocytes. Only recently, a microRNA (miR26a) was identified by our group as regulator of white and brite/beige adipocyte differentiation. However, to be applied as novel therapeutics, microRNAs need proper delivery systems to achieve efficient intracellular uptake.
EAS16-0571, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: ADIPOSE TISSUE. OVARIECTOMY AFFECTS SUBSTRATE UTILIZATION IN BROWN ADIPOSE TISSUE AND INDUCES LIVER DICARBONYL STRESS IN RATS J. Trnovska, H. Malinska, V. Skop, L. Kazdova. Institute for Clinical and Experimental Medicine, Center for Experimental medicine, Prague, Czech Republic Objectives: Postmenopausal metabolic syndrome may leads to increase in body weight, visceral obesity, insulin resistance, fatty liver and type 2 diabetes. Important player in substrate utilization is brown adipose tissue (BAT). BAT takes up and dissipates energy substrates that are present in excess in metabolic syndrome. We investigated the effects of ovariectomy (OVX) on the substrate utilization in BAT and white adipose tissue (WAT) and liver carbonyl and oxidative stress. Methods: OVX and shame-operated female Wistar rats were fed a standard diet for 4 months after OVX. 14C-palmitic acid and 14C-U-glucose oxidation and incorporation into lipid, and lipolysis, were measured in the visceral WAT and interscapular BAT ex vivo. The concentrations of methylglyoxal and glutathione in the liver were determined using the HPLCmethod with fluorescence detection. Results: OVX rats gained weight +15% compared to controls. Insulin sensitivity of white visceral adipose and muscle tissue was significantly decreased (WAT: -83%;p<0.05 and muscle: 60%;p˂0.01) in OVX rats. Severe hepatic triglycerides accumulation (+57%;p<0.001) in OVX rats associated with significantly elevated level of methylglyoxal (+57%;p˂0.01) may have contributed to the development of liver steatosis. Ovariectomy led to impaired balance GSH/GSSG (15.4±1.3vs.28.4±1.4;p˂0.01). BAT of OVX rats exhibited a reduced fatty acid oxidation (-137%;p<0.05), lipogenesis (-36%;p<0.05) and decreased lipolysis (-36%;p<0.05).