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Gender differences in lipid metabolism
Abstracts / Chemistry and Physics of Lipids xxx (2008) xxx–xxx
11
PL 15
SO 12
Gender differences in lipid metabolism
Differential effects in vivo of chronic PPAR activation on the myocardial subcellular distribution of FAT/CD36 and FABPpm
Bente Kiens Muscle Research Centre (CMRC) Institute of Exercise and Sport Sciences, University of Copenhagen, Molecular Physiology, Copenhagen, Denmark Women generally have a higher percentage of body fat than men and furthermore differences in fat distribution between men and women provide evidence of gender related differences in wholebody lipid metabolism. On the other hand, in skeletal muscle lipids are utilized and also stored and the impact of skeletal muscle lipid metabolism on whole-body energy homeostasis and lipid metabolism is important to consider. There is increasing evidence of gender related differences in skeletal muscle lipid metabolism. A significantly higher content of intramyocellular triacylglycerol (IMTG) is found in women compared with matched males. The higher IMTG content in females seems to be due to the higher content of type 1 muscle fibres in females but also due to a higher body fat percentage. There is also abundant evidence that the proportion of energy derived from lipids during submaximal exercise is higher in women than in men, irrespective of fitness level. Furthermore, females use IMTG as energy substrate to a much larger extent during submaximal exercise than males. This might indicate that the turnover of IMTG is higher in females than in males. The increased utilization of IMTG during exercise in females than in males seems to be due to the higher protein expression of hormone sensitive lipase (HSL) in skeletal muscle in females than in males (Roepstorff et al., 2006). Besides the findings of a higher HSL protein expression in skeletal muscle in females, there are robust findings of higher mRNA and protein abundance for several other components of the fat-oxidation pathway in skeletal muscle from the lipid transporters to mitochondrial enzymes in females compared with males. This is consistent with substrate oxidation data. It is evident from studies in both rodents and humans that lipids induce insulin resistance. Insulin sensitivity on a whole-body level is higher in women compared with matched males. Skeletal muscle plays an important role in insulin stimulated glucose uptake and the higher insulin sensitivity obtained in females is also reflected in a higher insulin stimulated glucose uptake in skeletal muscle in females than in males which may partly be explained by the higher oxidising capacity in skeletal muscle in females. Capillarisation in skeletal muscle is more dense in females than in males resulting in a better perfusion of the tissue and moreover the muscle fibre type distribution differs between genders, as females have more of the oxidative type 1 fibres than males. This gender related difference in skeletal muscle morphology can also add to the improved insulin sensitivity in females than in males but also to the gender differences in concentrations of circulating lipids and lipoproteins, at least in the premenopausal woman. Reference Roepstorff, C., Donsmark, M., Thiele, M., Vistisen, B., Stewart, G., Vissing, K., Schjerling, P., Hardie, D.G., Galbo, H., Kiens, B., 2006. Am. J. Physiol. Endocrinol. Metab. 291, E1106–E1114.
doi:10.1016/j.chemphyslip.2008.05.029
Adrian Chabowski, Ewa Harasim, Agnieszka Kalinowska, ´ Jan Gorski Department of Physiology, Medical University of Bialystok, Poland Peroxisome proliferator-activated receptors (PPAR␣, /␦ and ␥) are ligand-activated transcription factors highly involved in the regulation of the expression of a number of genes encoding proteins participating in fatty acid transmembrane transport. Key fatty acid transport proteins in heart include fatty acid translocase (FAT/CD36) and plasma membrane associated fatty acid binding protein (FABPpm). We investigated the effects of chronic stimulation of different PPAR isoforms on the redistribution of fatty acid transport proteins. The animals (male Wistar rats) were divided into 4 groups: (1) control, and treated for two weeks with a selective (2) PPAR␣ agonist, WY-14643, (3) PPAR␥ agonist, pioglitazone, (4) PPAR /␦ agonist, GW0742. Chronic PPAR␣ activation induced redistribution of only FAT/CD36 from an intracellular pool (LDM: −25%, p < 0.05) to the plasma membranes (PM: +33%, p < 0.05) as FABPpm expression remained constant (LDM: −5% and PM: +6%, p > 0.05). Treatment with PPAR/␦ agonist increased translocation of both FAT/CD36 and FABPpm to the plasma membranes (PM: +55% and +15%, p < 0.05, respectively) while concomitantly reducing their content in the intracellular fraction (LDM: −45% and −10%, p < 0.05, respectively). In contrast, PPAR␥ activation did not alter the expressions of both FAT/CD36 and FABPpm in either PM (+15% and +7%, p > 0.05, respectively) or LDM (−10% and +5%, %, p > 0.05, respectively). In parallel, we also observed no change in myocardial FA oxidation followed PPAR␥ activation, a small but constant increase after PPAR␣ stimulation (+7%, p = 0.09) and significantly increased FA oxidation with PPAR/␦ agonist treatment (+56%, p < 0.05). Accordingly, in perfused hearts stimulated by PPAR␣ and PPAR␥ agonists we did not observe significant changes in the incorporation of radiolabelled palmitate into TAG fraction, however, there was a significant increase in the radioactivity in this myocardial lipid fraction after PPAR/␦ activation (+34%, p < 0.05). doi:10.1016/j.chemphyslip.2008.05.030 SO 13 Stearoyl-CoA desaturase 1 deficiency increases glucose utilization in the heart Pawel Dobrzyn 1 , James M. Ntambi 2 , Agnieszka Dobrzyn 1 1
Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland 2 Department of Biochemistry, University of Wisconsin-Madison, Madison, USA Background: Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated fatty acids mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. Hypothesis/objectives: Since SCD1−/− mice have increased fatty acid (FA) oxidation in liver, skeletal muscle and brown adipose tissue, we hypothesized that substrate utilization in the heart would also be affected by SCD1 deficiency. Methods: The experiments were carried out on the twelveweek-old SCD1+/+ and SCD1−/− male mice. 2-deoxyglucose uptake in the heart was measured in vivo. The rate of FA and glucose oxi-
CPL 3739 1–20
11
PL 15
SO 12
Gender differences in lipid metabolism
Differential effects in vivo of chronic PPAR activation on the myocardial subcellular distribution of FAT/CD36 and FABPpm
Bente Kiens Muscle Research Centre (CMRC) Institute of Exercise and Sport Sciences, University of Copenhagen, Molecular Physiology, Copenhagen, Denmark Women generally have a higher percentage of body fat than men and furthermore differences in fat distribution between men and women provide evidence of gender related differences in wholebody lipid metabolism. On the other hand, in skeletal muscle lipids are utilized and also stored and the impact of skeletal muscle lipid metabolism on whole-body energy homeostasis and lipid metabolism is important to consider. There is increasing evidence of gender related differences in skeletal muscle lipid metabolism. A significantly higher content of intramyocellular triacylglycerol (IMTG) is found in women compared with matched males. The higher IMTG content in females seems to be due to the higher content of type 1 muscle fibres in females but also due to a higher body fat percentage. There is also abundant evidence that the proportion of energy derived from lipids during submaximal exercise is higher in women than in men, irrespective of fitness level. Furthermore, females use IMTG as energy substrate to a much larger extent during submaximal exercise than males. This might indicate that the turnover of IMTG is higher in females than in males. The increased utilization of IMTG during exercise in females than in males seems to be due to the higher protein expression of hormone sensitive lipase (HSL) in skeletal muscle in females than in males (Roepstorff et al., 2006). Besides the findings of a higher HSL protein expression in skeletal muscle in females, there are robust findings of higher mRNA and protein abundance for several other components of the fat-oxidation pathway in skeletal muscle from the lipid transporters to mitochondrial enzymes in females compared with males. This is consistent with substrate oxidation data. It is evident from studies in both rodents and humans that lipids induce insulin resistance. Insulin sensitivity on a whole-body level is higher in women compared with matched males. Skeletal muscle plays an important role in insulin stimulated glucose uptake and the higher insulin sensitivity obtained in females is also reflected in a higher insulin stimulated glucose uptake in skeletal muscle in females than in males which may partly be explained by the higher oxidising capacity in skeletal muscle in females. Capillarisation in skeletal muscle is more dense in females than in males resulting in a better perfusion of the tissue and moreover the muscle fibre type distribution differs between genders, as females have more of the oxidative type 1 fibres than males. This gender related difference in skeletal muscle morphology can also add to the improved insulin sensitivity in females than in males but also to the gender differences in concentrations of circulating lipids and lipoproteins, at least in the premenopausal woman. Reference Roepstorff, C., Donsmark, M., Thiele, M., Vistisen, B., Stewart, G., Vissing, K., Schjerling, P., Hardie, D.G., Galbo, H., Kiens, B., 2006. Am. J. Physiol. Endocrinol. Metab. 291, E1106–E1114.
doi:10.1016/j.chemphyslip.2008.05.029
Adrian Chabowski, Ewa Harasim, Agnieszka Kalinowska, ´ Jan Gorski Department of Physiology, Medical University of Bialystok, Poland Peroxisome proliferator-activated receptors (PPAR␣, /␦ and ␥) are ligand-activated transcription factors highly involved in the regulation of the expression of a number of genes encoding proteins participating in fatty acid transmembrane transport. Key fatty acid transport proteins in heart include fatty acid translocase (FAT/CD36) and plasma membrane associated fatty acid binding protein (FABPpm). We investigated the effects of chronic stimulation of different PPAR isoforms on the redistribution of fatty acid transport proteins. The animals (male Wistar rats) were divided into 4 groups: (1) control, and treated for two weeks with a selective (2) PPAR␣ agonist, WY-14643, (3) PPAR␥ agonist, pioglitazone, (4) PPAR /␦ agonist, GW0742. Chronic PPAR␣ activation induced redistribution of only FAT/CD36 from an intracellular pool (LDM: −25%, p < 0.05) to the plasma membranes (PM: +33%, p < 0.05) as FABPpm expression remained constant (LDM: −5% and PM: +6%, p > 0.05). Treatment with PPAR/␦ agonist increased translocation of both FAT/CD36 and FABPpm to the plasma membranes (PM: +55% and +15%, p < 0.05, respectively) while concomitantly reducing their content in the intracellular fraction (LDM: −45% and −10%, p < 0.05, respectively). In contrast, PPAR␥ activation did not alter the expressions of both FAT/CD36 and FABPpm in either PM (+15% and +7%, p > 0.05, respectively) or LDM (−10% and +5%, %, p > 0.05, respectively). In parallel, we also observed no change in myocardial FA oxidation followed PPAR␥ activation, a small but constant increase after PPAR␣ stimulation (+7%, p = 0.09) and significantly increased FA oxidation with PPAR/␦ agonist treatment (+56%, p < 0.05). Accordingly, in perfused hearts stimulated by PPAR␣ and PPAR␥ agonists we did not observe significant changes in the incorporation of radiolabelled palmitate into TAG fraction, however, there was a significant increase in the radioactivity in this myocardial lipid fraction after PPAR/␦ activation (+34%, p < 0.05). doi:10.1016/j.chemphyslip.2008.05.030 SO 13 Stearoyl-CoA desaturase 1 deficiency increases glucose utilization in the heart Pawel Dobrzyn 1 , James M. Ntambi 2 , Agnieszka Dobrzyn 1 1
Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland 2 Department of Biochemistry, University of Wisconsin-Madison, Madison, USA Background: Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated fatty acids mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. Hypothesis/objectives: Since SCD1−/− mice have increased fatty acid (FA) oxidation in liver, skeletal muscle and brown adipose tissue, we hypothesized that substrate utilization in the heart would also be affected by SCD1 deficiency. Methods: The experiments were carried out on the twelveweek-old SCD1+/+ and SCD1−/− male mice. 2-deoxyglucose uptake in the heart was measured in vivo. The rate of FA and glucose oxi-
CPL 3739 1–20