Effect of metformin on glucose and fatty acid utilization in brown adipose tissue

Effect of metformin on glucose and fatty acid utilization in brown adipose tissue

e46 Abstracts / Atherosclerosis 241 (2015) e32ee71 Results: At baseline, CRP surprisingly was significantly higher in nonobese subjects (n¼1,367) tha...

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Abstracts / Atherosclerosis 241 (2015) e32ee71

Results: At baseline, CRP surprisingly was significantly higher in nonobese subjects (n¼1,367) than obese individuals (n¼364)(0.6±1.5 vs. 0.5±0.8 mg/dl; p Conclusions: From the results of this large 10-year prospective cohort study we conclude that obesity significantly modulates the power of CRP to predict cardiovascular event risk among angiographied coronary patients.

EAS-0012. A DIET LOW IN SUGAR REDUCES THE PRODUCTION OF ATHEROGENIC LIPOPROTEINS IN MEN WITH HIGH LIVER FAT M. Umpleby 1, F. Shojaee-Moradie 1, B. Fielding 1, X. Li 1, C. Isherwood 1, N. Jackson 1, G. Wilinska 2, R. Hovorka 2, J. Bell 3, E.L. Thomas 3, J. Wright 1, G.S. Frost 3, B. Griffin 1. 1 Nutritional Sciences, University of Surrey, Guildford, United Kingdom; 2 Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; 3 Division of Diabetes Endocrinology and Metabolism, Imperial College London, London, United Kingdom Aim: To determine how dietary sugar promotes the formation of an atherogenic lipoprotein phenotype by studying the effects of high and low sugar diets on lipoprotein kinetics. Methods: Two groups of men at risk of metabolic syndrome, with low liver fat (LLF; <5%) (n¼14) or high liver fat (HLF; >5%) [BAG1] (n¼11), were randomised to a cross-over intervention with high and low sugar diets (HSD; 26% energy or LSD; 6% energy) for 12 weeks. ApoB production (PR) and fractional catabolic rates (FCR) of lipoprotein fractions (VLDL1, VLDL2, IDL, LDL2 and LDL3 apolipoproteinB (apoB)) were measured by constant infusion of 13C-leucine and mathematical modelling. Results: In post-dietary comparisons (LSD v HSD), liver fat was lower after the LSD in both groups (HLF, p¼0.01; LLF, p¼0.008). In LLF men, VLDL1 apoB, TG and cholesterol concentration, LDL3 apoB concentration and VLDL1 apoB PR were lower (all p <0.05) after a LSD whilst VLDL1 apoB FCR and VLDL2, IDL and LDL apoB kinetics were not different. In HLF men, plasma TG was lower (p<0.04), but VLDL1 and VLDL2 apoB kinetics were unchanged after the LSD but IDL apoB, TG and cholesterol concentration, IDL apoB PR and LDL3 apoB PR and FCR were lower (All p¼0.05). Small dense LDL cholesterol and oxidized LDL were lower in both groups after the LSD (HLF: p¼0.02, p¼0.08; LLF: p¼0.02, p<0.02 respectively). Conclusion: Men with HLF and LLF respond differently to dietary sugar. A LSD can reduce the production of atherogenic lipoproteins in men with HLF.

EAS-0143. EFFECT OF METFORMIN ON GLUCOSE AND FATTY ACID UTILIZATION IN BROWN ADIPOSE TISSUE J. Trnovska, V. Skop, H. Malinska, L. Kazdova. Center for experimental medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Aim: Growing evidence indicates that metformin, in addition to its well-recognized antihyperglycemic properties, also reduces total body and abdominal fat, but the mechanisms are still unclear. Brown adipose tissue (BAT) plays an important role in triglyceride and glucose utilization for thermoregulation and thus could prevent obesity, ectopic fat accumulation, and associated metabolic disturbances. The aim of this study was to investigate if metformin increase glucose and fatty acid utilization in BAT, and ameliorate related parameters of metabolic syndrome. Methods: Male Wistar rats (age: 8 months) were fed a standard diet (SD) or SD enriched by metformin (SD+Mf) in a dose: 300 mg/kg b.wt./day for 4 weeks. Lipolysis, 14C-U-palmitic acid and 14C-U-glucose oxidation and incorporation into lipids were measured in the interscapular BAT ex vivo.

Results: Metformin significantly decreased body weight (-25 %, P<0.001), adiposity (-61 %, P<0.002), serum triglycerides (-48 %, P<0.03) and ectopic accumulation of triglycerides in liver (-72 %, P<0.02), heart (-66 %, P<0.03), aorta (-48 %, P<0.01) and diaphragm (-80 %, P<0.01). Metformin increased lipolysis (+47 %, P<0.01), palmitic acid oxidation (+45 %, P<0.03) and incorporation into BAT lipids (+26 %, P<0.01). There were not significant differences in glucose oxidation between groups but basal (+61 %, P<0.01) and insulin stimulated (+60 %, P<0.01) incorporation of glucose into BAT lipids was higher after metformin treatment. Conclusion: Results indicate that metformin-induced increase of lipid and glucose utilization in BAT may participate in the improvement of metabolic syndrome disorders. Supported by the grant GACR P303/13-04420S

EAS-0149. FAST REGRESSION OF CAROTID INTIMA-MEDIA THICKNESS AND CARDIOVASCULAR RISK FACTORS IN PATIENTS PRE- AND POSTBARIATRIC SURGERY J. Matos-Souza, G. De Rossi, W. Cirillo, W. Nadruz, Jr., O.R. Coelho. Clinical, Faculty of Medical Sciences, Campinas, Brazil Purpose: Obesity is associated with cardiovascular risk factors (CVRFs), such as hypertension, hypertriglyceridemia, and low levels of high-density cholesterol (HDL-C). In obese patients with a body mass index (BMI) of 40 kg/m2 or 35-40 kg/m2 associated with CVRFs, bariatric surgery promove significant weight loss and showed reduction on CVRFs. Carotid intima-media thickness (C-IMT) is widely acept as an indicator of atherosclerosis, and used to be correlated with severals CVRFs. Our objective was to correlate C-IMT with CVRFs before (baseline data) and after surgery, and to observe whether weight loss is followed by a regression of C-IMT. Methods: Fifty four patients who had undergone bariatric surgery participated in this study. Assessments were carried out on the baseline date, and 1, 2, 6, and 12 months after surgery. CVRFs analyzed were: total cholesterol (TC) levels, HDL-C, triglycerides to HDL-C ratio (TG/ HDL-C) and fasting plasma glucose. C-IMT was measured by B-mode ultrasound. Results: One month after surgery, we found a significant reduction in CIMT (p < 0.001), which was significantly correlated with fasting plasma glucose, low-density cholesterol (LDL-C) (p < 0.001), BMI (p < 0.001) and waist circunference (p < 0.05). The reduction in C-IMT is significantly after 2, 6 and 12 months (p<0,001) Conclusion: The impact achieved with bariatric surgery resulted in fast regression of C-IMT. This regression could be observed at 1, 2 and 6 months following surgery, with an sustained benefit at 12 months. This finding was correlated with a reduction in LDL-C levels, fasting plasma glucose, BMI and waist circunference.

EAS-0471. STAT3 INHIBITION INDUCES PCSK9 IN HEPATIC CELL LINE: POSSIBLE INVOLVEMENT IN HYPERTRIGLYCERIDEMIA ASSOCIATED WITH INSULIN RESISTANCE C. Ricci, M. Ruscica, C. Macchi, P. Magni, A. Corsini, N. Ferri. Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, Italy PCSK9 regulates the circulating LDL-cholesterol levels by inducing LDLR degradation. However, PCSK9 levels are positively correlated with insulin resistance, liver steatosis and plasma VLDL-TG concentrations. This evidence suggests that PCSK9 could be implicated in lipid homeostasis. Chronic inflammation, associated with elevated circulating cytokines, and hepatic overexpression of suppressor of cytokine signaling (SOCS) proteins, are major determinants of hypertriglyceridemia associated to insulin resistance. In the present study, we have investigated the role of SOCS3 in the transcriptional regulation of PCSK9 in HepG2 cells. Forced overexpression of SOCS3 determined the abrogation of STAT3