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Obesity and insulin resistance is associated with lower atp binding cassette transporter A1 (Abca1) expression in visceral adipose tissue
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Abstracts / Atherosclerosis 263 (2017) e111ee282
significant increase of IL-6, TNFalpha, MSR1, CL-P1 and CXCL16 mRNA expression. In differentiated adipocytes from MO, hypoxia produced a decrease of CL-P1 and an increase of CXCL16 mRNA expression. Conclusions: In this study we demonstrate that hypoxia produced an increase of inflammation and of different scavenger receptors in adipocytes. Acknowledgment This work was supported in part by grants from Instituto de Salud Carlos III (CP13/00188), Spain. This study has been co-funded by FEDER funds.
PO464. OBESITY AND INSULIN RESISTANCE IS ASSOCIATED WITH LOWER ATP BINDING CASSETTE TRANSPORTER A1 (ABCA1) EXPRESSION IN VISCERAL ADIPOSE TISSUE Vinnyfred Vincent1, Himani Thakkar1, Sandeep Aggarwal2, Asit Ranjan Mridha3, Lakshmy Ramakrishnan4, Archna Singh1. 1 All India Institute of Medical Sciences, Department of Biochemistry, New Delhi, India; 2 All India Institute of Medical Sciences, Department of Surgery, New Delhi, India; 3 All India Institute of Medical Sciences, Department of Pathology, New Delhi, India; 4 All India Institute of Medical Sciences, Department of Cardiac Biochemistry, New Delhi, India Aim: Adipose tissue dysfunction is at the centre of metabolic dysfunction associated with obesity. Adipose tissue cholesterol imbalance is postulated to be one of the causes for this dysfunction. ABCA1 is the major route for cholesterol efflux from peripheral tissues to HDL. We explore the role of ABCA1 in adipose tissue in modulating metabolic derangements associated with obesity. Methods: This exploratory study amongst obese and non-obese individuals compared the expression of ABCA1, adiponectin and GLUT4 using quantitative real-time PCR and immunohistochemistry. Biochemical parameters were estimated and used for calculation of insulin resistance markers (HOMA-IR and Adipo-IR). Results: Expression levels of ABCA1, adiponectin and GLUT4 were significantly lower in visceral adipose tissue in obese (BMI: 44.78±5.66 kg/m2, n:35) compared to non-obese (BMI: 22.43±1.8 kg/m2, n:30) individuals. Subcutaneous adipose tissue did not show any difference in the expression of ABCA1 or adiponectin. There was significantly higher insulin resistance in obese individuals compared to non-obese individuals. Obese individuals with insulin resistance had lower ABCA1 expression (0.96±0.40 vs 0.61±0.19) in visceral adipose tissue and higher non-esterified fatty acid (NEFA) levels (0.61±0.05 mmol/l vs 0.42±0.04 mmol/l) in circulation compared to obese insulin sensitive individuals. No significant correlation was observed between ABCA1 expression and HDL-C levels. Conclusions: ABCA1 expression in adipose tissue is not likely to contribute significantly to HDL cholesterol levels in circulation. However, ABCA1 expression in visceral adipose tissue could be involved in the modulation of insulin sensitivity since a higher ABCA1 expression was seen in visceral adipose tissue amongst obese but insulin sensitive individuals.
PO465. EFFECT OF CANAGLIFLOZIN ON VISCERAL FAT AREA AND HEART RATE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS Ryoko Mitsutake. Fukuoka University Chikushi Hospital, Department of Cardiology, Chikushino, Japan Aim: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, offers greater glycemic control, as well as important additional benefits such as weight loss and blood pressure reductions. Methods: We analyzed the visceral fat area as assessed by computed tomography, HbA1c, blood glucose, lipid profile, blood pressure and pulse rate before and 3 months after administration of canagliflozin in patients with uncontrolled type 2 diabetes mellitus. Results: In this study, 7 patients (5 male and 2 female, mean 61 years) were enrolled. Of the patients, 4 patients had metoformin and 5 patients had DPP4 inhibitor in combination with canagliflozin. Reductions in HbA1c and blood glucose with canagliflozin were -0.6 % and 44 mg/dl, respectively, however there was no statistically significant reduction in
both HbA1c and blood glucose (p¼0.0863 and p¼0.1485) in this period. The visceral fat area and pulse rate were significantly reduced (p¼0.0008 and p¼0.0162) 3 months after treatment with canagliflozin. Conclusions: In conclusion, canagliflozin improved not only glycemic control but also reduction of visceral fat area as assessed by computed tomography. SGLT2 inhibitor might be up-stream treatment for type 2 diabetes mellitus with metabolic syndrome which activates sympathetic nerve. PO466. EARLY LIFE DETERMINANTS OF ADIPOSITY AMONG CHILDREN IN INDIA Prerna Bhasin1, Satwanti Kapoor2. 1 Inspire Analytics Ltd, London, United Kingdom; 2 University Of Delhi, Delhi, India Aim: The study investigates the hypothesis that pre-, peri- and postpartum risk factors have a causal effect on the risk of adiposity at age 6 to 9 among Indian children. Methods: The study is a school-based, cross-sectional survey in an urban setting (New Delhi) of India. The sample size included 727 males with 730 females of metropolitan area and aged 6-9 years. As the study examines pre-, peri- and post-natal risk factors, focusing on critical periods and temporal relationships of these exposures in relation to development of obesity, life course health (LCH) model was used. Anthropometric measurements, life-style indicators, socio-economic status were measured and quantified with help of questionnaires. Lifestyle factors and maternal characteristics were adjusted for confounding effect. Results: The results revealed, among pre-natal factors for overweight or obesity status, adjusted odds ratio for presence of gestational complications was 2.11 (95% CI 1.98-2.51) and that for smoking/drinking during gestation was 2.01 (95% CI 1.34-2.47), and gestational weight gain > 16.0 Kgs during was accompanied with odds of 1.23 (95% CI 1.11-2.02). Odds ratio for peri-natal factors was nearly 1.90 (95% CI 1.51-3.02) for caesarian section, and for the birth-weight categories, a U-shaped association was revealed with risk for obesity. Conclusions: Estimation of risk of adiposity reveals that pre-partum factors are relatively stronger predictors than peri- or post-partum exposures. We recommend that the policies should not only provide medical care during ante- and post-natal period but focus on course of life as a whole and intervene at sensitive periods to curb the obesity epidemic. Poster session: diabetes, insulin resistance, and nash PO467. INSULIN RESISTANCE AND LOW SERUM ADIPONECTIN LEVEL AS A RISK FACTORS OF ATHEROSCLEROSIS AND METABOLIC SYNDROME Belyaeva1, 2, Elena Bazhenova1, Olga Ekaterina Polyakova1, Olga Berkovich1, Aelita Berezina1, 2, Valery Ionin1, Anna Bakulina1, Elena Baranova1, 2, Eugenie Shlyakhto1, 2. 1 Pavlov First Saint-Petersburg Federal State Medical University, Saint-Petersburg, Russia; 2 Federal Almazov NorthWest Medical Research Centre, Saint-Petersburg, Russia Aim: To evaluate insulin resistance and serum adiponectin levels in hypertensive patients with abdominal obesity (AO). Methods: 205 hypertensive patients aged 30-55 years (45,14±0,43y.) with AO, IDF (2005). 41% of patients were overweight (BMI 28,01±0,14 kg/m2), 59% were obese (BMI 35,11±0,36 kg/m2). 20 normotensive subjects with BMI<25 kg/m2 formed control group. Adiponectin and insulin levels were evaluated by ELISA (DRG, USA). Fasting plasma glucose was detected by standard biochemical method. To evaluate insulin resistance Homeostasis Model Assessment was used (HOMA-IR). Results: Serum adiponectin level in patients with AO was 19,32±1,24 mg/ ml, and it did not differ in overweight and obese patients (20,42±1,21 mg/ ml, 19,19±0,74 mg/ml, accordingly, p>0,05), but it was lower than in healthy controls 25,93±0,88 mg/ml, p<0,05. Serum adiponectin levels were higher in women than in men (21,74±0,74 mg/ml and 16,62±1,01 mg/ml accordingly, p¼0,001). HOMA-IR in patients with AO was higher in patients with BMI>30 kg/m2 than in overweight subjects (6,30±0,69 vs 3,41, p¼0,001) and in hypertensive patients when compared to normotensive subjects (5,82±0,67 vs 4,02, p¼0,008). Correlations were revealed between HOMA-
Abstracts / Atherosclerosis 263 (2017) e111ee282
significant increase of IL-6, TNFalpha, MSR1, CL-P1 and CXCL16 mRNA expression. In differentiated adipocytes from MO, hypoxia produced a decrease of CL-P1 and an increase of CXCL16 mRNA expression. Conclusions: In this study we demonstrate that hypoxia produced an increase of inflammation and of different scavenger receptors in adipocytes. Acknowledgment This work was supported in part by grants from Instituto de Salud Carlos III (CP13/00188), Spain. This study has been co-funded by FEDER funds.
PO464. OBESITY AND INSULIN RESISTANCE IS ASSOCIATED WITH LOWER ATP BINDING CASSETTE TRANSPORTER A1 (ABCA1) EXPRESSION IN VISCERAL ADIPOSE TISSUE Vinnyfred Vincent1, Himani Thakkar1, Sandeep Aggarwal2, Asit Ranjan Mridha3, Lakshmy Ramakrishnan4, Archna Singh1. 1 All India Institute of Medical Sciences, Department of Biochemistry, New Delhi, India; 2 All India Institute of Medical Sciences, Department of Surgery, New Delhi, India; 3 All India Institute of Medical Sciences, Department of Pathology, New Delhi, India; 4 All India Institute of Medical Sciences, Department of Cardiac Biochemistry, New Delhi, India Aim: Adipose tissue dysfunction is at the centre of metabolic dysfunction associated with obesity. Adipose tissue cholesterol imbalance is postulated to be one of the causes for this dysfunction. ABCA1 is the major route for cholesterol efflux from peripheral tissues to HDL. We explore the role of ABCA1 in adipose tissue in modulating metabolic derangements associated with obesity. Methods: This exploratory study amongst obese and non-obese individuals compared the expression of ABCA1, adiponectin and GLUT4 using quantitative real-time PCR and immunohistochemistry. Biochemical parameters were estimated and used for calculation of insulin resistance markers (HOMA-IR and Adipo-IR). Results: Expression levels of ABCA1, adiponectin and GLUT4 were significantly lower in visceral adipose tissue in obese (BMI: 44.78±5.66 kg/m2, n:35) compared to non-obese (BMI: 22.43±1.8 kg/m2, n:30) individuals. Subcutaneous adipose tissue did not show any difference in the expression of ABCA1 or adiponectin. There was significantly higher insulin resistance in obese individuals compared to non-obese individuals. Obese individuals with insulin resistance had lower ABCA1 expression (0.96±0.40 vs 0.61±0.19) in visceral adipose tissue and higher non-esterified fatty acid (NEFA) levels (0.61±0.05 mmol/l vs 0.42±0.04 mmol/l) in circulation compared to obese insulin sensitive individuals. No significant correlation was observed between ABCA1 expression and HDL-C levels. Conclusions: ABCA1 expression in adipose tissue is not likely to contribute significantly to HDL cholesterol levels in circulation. However, ABCA1 expression in visceral adipose tissue could be involved in the modulation of insulin sensitivity since a higher ABCA1 expression was seen in visceral adipose tissue amongst obese but insulin sensitive individuals.
PO465. EFFECT OF CANAGLIFLOZIN ON VISCERAL FAT AREA AND HEART RATE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS Ryoko Mitsutake. Fukuoka University Chikushi Hospital, Department of Cardiology, Chikushino, Japan Aim: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, offers greater glycemic control, as well as important additional benefits such as weight loss and blood pressure reductions. Methods: We analyzed the visceral fat area as assessed by computed tomography, HbA1c, blood glucose, lipid profile, blood pressure and pulse rate before and 3 months after administration of canagliflozin in patients with uncontrolled type 2 diabetes mellitus. Results: In this study, 7 patients (5 male and 2 female, mean 61 years) were enrolled. Of the patients, 4 patients had metoformin and 5 patients had DPP4 inhibitor in combination with canagliflozin. Reductions in HbA1c and blood glucose with canagliflozin were -0.6 % and 44 mg/dl, respectively, however there was no statistically significant reduction in
both HbA1c and blood glucose (p¼0.0863 and p¼0.1485) in this period. The visceral fat area and pulse rate were significantly reduced (p¼0.0008 and p¼0.0162) 3 months after treatment with canagliflozin. Conclusions: In conclusion, canagliflozin improved not only glycemic control but also reduction of visceral fat area as assessed by computed tomography. SGLT2 inhibitor might be up-stream treatment for type 2 diabetes mellitus with metabolic syndrome which activates sympathetic nerve. PO466. EARLY LIFE DETERMINANTS OF ADIPOSITY AMONG CHILDREN IN INDIA Prerna Bhasin1, Satwanti Kapoor2. 1 Inspire Analytics Ltd, London, United Kingdom; 2 University Of Delhi, Delhi, India Aim: The study investigates the hypothesis that pre-, peri- and postpartum risk factors have a causal effect on the risk of adiposity at age 6 to 9 among Indian children. Methods: The study is a school-based, cross-sectional survey in an urban setting (New Delhi) of India. The sample size included 727 males with 730 females of metropolitan area and aged 6-9 years. As the study examines pre-, peri- and post-natal risk factors, focusing on critical periods and temporal relationships of these exposures in relation to development of obesity, life course health (LCH) model was used. Anthropometric measurements, life-style indicators, socio-economic status were measured and quantified with help of questionnaires. Lifestyle factors and maternal characteristics were adjusted for confounding effect. Results: The results revealed, among pre-natal factors for overweight or obesity status, adjusted odds ratio for presence of gestational complications was 2.11 (95% CI 1.98-2.51) and that for smoking/drinking during gestation was 2.01 (95% CI 1.34-2.47), and gestational weight gain > 16.0 Kgs during was accompanied with odds of 1.23 (95% CI 1.11-2.02). Odds ratio for peri-natal factors was nearly 1.90 (95% CI 1.51-3.02) for caesarian section, and for the birth-weight categories, a U-shaped association was revealed with risk for obesity. Conclusions: Estimation of risk of adiposity reveals that pre-partum factors are relatively stronger predictors than peri- or post-partum exposures. We recommend that the policies should not only provide medical care during ante- and post-natal period but focus on course of life as a whole and intervene at sensitive periods to curb the obesity epidemic. Poster session: diabetes, insulin resistance, and nash PO467. INSULIN RESISTANCE AND LOW SERUM ADIPONECTIN LEVEL AS A RISK FACTORS OF ATHEROSCLEROSIS AND METABOLIC SYNDROME Belyaeva1, 2, Elena Bazhenova1, Olga Ekaterina Polyakova1, Olga Berkovich1, Aelita Berezina1, 2, Valery Ionin1, Anna Bakulina1, Elena Baranova1, 2, Eugenie Shlyakhto1, 2. 1 Pavlov First Saint-Petersburg Federal State Medical University, Saint-Petersburg, Russia; 2 Federal Almazov NorthWest Medical Research Centre, Saint-Petersburg, Russia Aim: To evaluate insulin resistance and serum adiponectin levels in hypertensive patients with abdominal obesity (AO). Methods: 205 hypertensive patients aged 30-55 years (45,14±0,43y.) with AO, IDF (2005). 41% of patients were overweight (BMI 28,01±0,14 kg/m2), 59% were obese (BMI 35,11±0,36 kg/m2). 20 normotensive subjects with BMI<25 kg/m2 formed control group. Adiponectin and insulin levels were evaluated by ELISA (DRG, USA). Fasting plasma glucose was detected by standard biochemical method. To evaluate insulin resistance Homeostasis Model Assessment was used (HOMA-IR). Results: Serum adiponectin level in patients with AO was 19,32±1,24 mg/ ml, and it did not differ in overweight and obese patients (20,42±1,21 mg/ ml, 19,19±0,74 mg/ml, accordingly, p>0,05), but it was lower than in healthy controls 25,93±0,88 mg/ml, p<0,05. Serum adiponectin levels were higher in women than in men (21,74±0,74 mg/ml and 16,62±1,01 mg/ml accordingly, p¼0,001). HOMA-IR in patients with AO was higher in patients with BMI>30 kg/m2 than in overweight subjects (6,30±0,69 vs 3,41, p¼0,001) and in hypertensive patients when compared to normotensive subjects (5,82±0,67 vs 4,02, p¼0,008). Correlations were revealed between HOMA-