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Postprandial metabolism of apolipoprotein B48-containing particles in type 1 diabetes mellitus
86
Abstracts / Atherosclerosis Supplements 9 (2008) 83–102
(MUFA’s), polyunsaturated fatty acids (PUFA’s) or saturated fatty acids (SFA’s). Methodology: Six-week-old female C57BL/6J mouse were placed on diets containing either 20% (w/w) monounsaturated fatty acid (MUFA), polyunsaturated fatty acids (PUFA) or saturated fatty acids (SFA) for 12 weeks. Mice fed a diet containing 4% PUFA served as low-fat controls. Intracellular lipoprotein metabolism was determined using quantitative immunohistochemistry (IHC) or immunofluorescence microscopy (IFM) for apolipoprotein B and selective staining techniques. Results: Animals fed fat enriched diets showed marked accumulation of enterocytic lipids compared to low-fat fed controls. However, there were substantial differences depending on the type of fatty acid consumed. Animals given the PUFA enriched diet showed substantially less intracellular lipids accompanied by enhanced secretion into lacteals. The SFA’s fed mice had massive cytosolic lipids with little evidence of secretion into lymphatics. A similar response was seen in MUFA fed animals, although the effect was not as pronounced as for SFA fed mice. Conclusion: This study demonstrates that incorporation and secretion of dietary triglycerides as chylomicrons is dependent on the fatty acid composition. Polyunsaturated fatty acids are more rapidly processed within enterocytes than either MUFA’s or SFA’s.
accumulation in a free-living environment. ApoB48 concentrations were determined utilizing an adapted SDS-PAGE and immunoblotting technique. Fasting and postprandial concentrations of plasma glucose, triglycerides (TG), cholesterol, and serum insulin were also measured. Results: Fasting concentrations of plasma apoB48 (type 1 DM group: 22.8 ± 2.5 g/mL vs. control group: 11.6 ± 0.76 g/mL, p = 0.019) and postprandial apoB48 area under the curve (AUC) (222.9 ± 11.3 g/mL vs. control group: 155.4 ± 21.7, p = 0.012) were significantly greater in type 1 DM subjects compared to controls. Subjects with type 1 DM also demonstrated an elevated postprandial glucose AUC, and postprandial TG level at 6 h. There were no differences in fasting glucose, insulin and lipid parameters (low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol and TG), or postprandial insulin, cholesterol and TG AUC between type 1 DM subjects and controls. Conclusions: An abnormal postprandial chylomicron metabolism is a trait of individuals with type 1 DM even without evidence of traditional fasting dyslipidemia.
doi:10.1016/j.atherosclerosissup.2008.09.402
doi:10.1016/j.atherosclerosissup.2008.09.403
Postprandial metabolism of apolipoprotein containing particles in type 1 diabetes mellitus
B48-
J. Su ∗ , J. Lambert, E. Ryan, M.T. Clandinin, S.D. Proctor Metabolic and Cardiovascular Disease Laboratory, Alberta Institute for Human Nutrition and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada Background: Aberrant metabolism of intestinally derived apolipoprotein B48 (apoB48)-containing chylomicrons and their remnants, a known contributor to the development of atherosclerosis, has been described among individuals with coronary artery disease and type 2 diabetes mellitus (DM). However, little is known regarding postprandial lipoprotein metabolism in type 1 DM. Type 1 DM is associated with a 3-to 4-fold increase in cardiovascular disease (CVD) risk as compared with an age-matched non-diabetic population, despite no abnormalities of the fasting lipid profile. Therefore, the objective of this study was to investigate postprandial chylomicron metabolism in this population. Methods: Nine people (four men and five women) with brittle type 1 DM and four healthy controls (one man and three women) of similar age (type 1 DM group: 53.3 ± 3.3 years; control group: 46.5 ± 6.3) and BMI (type 1 DM group: 24.9 ± 1.2; control group: 23.1 ± 0.47) were enrolled. Blood was drawn at fasting, 2 and 4 h following breakfast, and 6 and 8 h following lunch to follow apoB48 metabolism and
Acknowledgements Support for this work was funded in part by CIHR, Canadian Diabetes Association and NSERC.
Friday—Plenary Seminar Intestinal lipoprotein overproduction in insulin resistant states: Focus on human studies G. Lewis University of Toronto, Toronto, Canada Triglyceride-rich lipoproteins (TRLs) derived from the intestine are increased in insulin resistant states both in the postprandial and fasted state and are associated with increased cardiovascular risk. Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs, but more recent studies have highlighted the fact that the production rate of apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and type 2 diabetes. This talk will review some of the key recent findings in the field, focusing on recent human studies from our laboratory. doi:10.1016/j.atherosclerosissup.2008.09.404
Abstracts / Atherosclerosis Supplements 9 (2008) 83–102
(MUFA’s), polyunsaturated fatty acids (PUFA’s) or saturated fatty acids (SFA’s). Methodology: Six-week-old female C57BL/6J mouse were placed on diets containing either 20% (w/w) monounsaturated fatty acid (MUFA), polyunsaturated fatty acids (PUFA) or saturated fatty acids (SFA) for 12 weeks. Mice fed a diet containing 4% PUFA served as low-fat controls. Intracellular lipoprotein metabolism was determined using quantitative immunohistochemistry (IHC) or immunofluorescence microscopy (IFM) for apolipoprotein B and selective staining techniques. Results: Animals fed fat enriched diets showed marked accumulation of enterocytic lipids compared to low-fat fed controls. However, there were substantial differences depending on the type of fatty acid consumed. Animals given the PUFA enriched diet showed substantially less intracellular lipids accompanied by enhanced secretion into lacteals. The SFA’s fed mice had massive cytosolic lipids with little evidence of secretion into lymphatics. A similar response was seen in MUFA fed animals, although the effect was not as pronounced as for SFA fed mice. Conclusion: This study demonstrates that incorporation and secretion of dietary triglycerides as chylomicrons is dependent on the fatty acid composition. Polyunsaturated fatty acids are more rapidly processed within enterocytes than either MUFA’s or SFA’s.
accumulation in a free-living environment. ApoB48 concentrations were determined utilizing an adapted SDS-PAGE and immunoblotting technique. Fasting and postprandial concentrations of plasma glucose, triglycerides (TG), cholesterol, and serum insulin were also measured. Results: Fasting concentrations of plasma apoB48 (type 1 DM group: 22.8 ± 2.5 g/mL vs. control group: 11.6 ± 0.76 g/mL, p = 0.019) and postprandial apoB48 area under the curve (AUC) (222.9 ± 11.3 g/mL vs. control group: 155.4 ± 21.7, p = 0.012) were significantly greater in type 1 DM subjects compared to controls. Subjects with type 1 DM also demonstrated an elevated postprandial glucose AUC, and postprandial TG level at 6 h. There were no differences in fasting glucose, insulin and lipid parameters (low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol and TG), or postprandial insulin, cholesterol and TG AUC between type 1 DM subjects and controls. Conclusions: An abnormal postprandial chylomicron metabolism is a trait of individuals with type 1 DM even without evidence of traditional fasting dyslipidemia.
doi:10.1016/j.atherosclerosissup.2008.09.402
doi:10.1016/j.atherosclerosissup.2008.09.403
Postprandial metabolism of apolipoprotein containing particles in type 1 diabetes mellitus
B48-
J. Su ∗ , J. Lambert, E. Ryan, M.T. Clandinin, S.D. Proctor Metabolic and Cardiovascular Disease Laboratory, Alberta Institute for Human Nutrition and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada Background: Aberrant metabolism of intestinally derived apolipoprotein B48 (apoB48)-containing chylomicrons and their remnants, a known contributor to the development of atherosclerosis, has been described among individuals with coronary artery disease and type 2 diabetes mellitus (DM). However, little is known regarding postprandial lipoprotein metabolism in type 1 DM. Type 1 DM is associated with a 3-to 4-fold increase in cardiovascular disease (CVD) risk as compared with an age-matched non-diabetic population, despite no abnormalities of the fasting lipid profile. Therefore, the objective of this study was to investigate postprandial chylomicron metabolism in this population. Methods: Nine people (four men and five women) with brittle type 1 DM and four healthy controls (one man and three women) of similar age (type 1 DM group: 53.3 ± 3.3 years; control group: 46.5 ± 6.3) and BMI (type 1 DM group: 24.9 ± 1.2; control group: 23.1 ± 0.47) were enrolled. Blood was drawn at fasting, 2 and 4 h following breakfast, and 6 and 8 h following lunch to follow apoB48 metabolism and
Acknowledgements Support for this work was funded in part by CIHR, Canadian Diabetes Association and NSERC.
Friday—Plenary Seminar Intestinal lipoprotein overproduction in insulin resistant states: Focus on human studies G. Lewis University of Toronto, Toronto, Canada Triglyceride-rich lipoproteins (TRLs) derived from the intestine are increased in insulin resistant states both in the postprandial and fasted state and are associated with increased cardiovascular risk. Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs, but more recent studies have highlighted the fact that the production rate of apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and type 2 diabetes. This talk will review some of the key recent findings in the field, focusing on recent human studies from our laboratory. doi:10.1016/j.atherosclerosissup.2008.09.404