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PP226-MON MICROGEL FORMATION OF WHEY PROTEIN REDUCES ITS INSULINOGENIC INDEX WITHOUT MODIFYING GLYCEMIC RESPONSE IN HEALTHY MEN
Protein and amino acid metabolism II Results: The mice with whey based formula showed increased the levels of intermediates of TCA cycle and decreased intermediates of glycolytic pathway and accumulation of lactate, finally enhanced energy expenditure 1.5 fold compared to mice with casein formula. The inhibition of mTOR by rapamycin induced the activation of glycolytic pathway, inhibition TCA cycle, decreased energy expenditure of mitochondria. Using primary skeletal muscle cells, mTOR binds to VDAC and Bcl-xl and phosphorylates Bcl-xl. Conclusion: Whey protein prompts TCA cycle and increases energy expenditure via mTOR signaling. Disclosure of Interest: None Declared.
PP224-MON NUTRITIONAL STATUS IN CHILDREN WITH PHENYLKETONURIA H.N. Choong1 , B. Cochrane2 , J. Jones3 , P. Robinson4 , B. Schwahn4 , K. Gerasimidis1 . 1 Human Nutrition, University of Glasgow, 2 Department of Dietetics, 3 Department of Endocrinology, 4 Department of Inherited Disorders of Metabolism, NHS Greater Glasgow & Clyde, Glasgow, United Kingdom Rationale: There is a scarcity of studies which characterise and examine predictors of nutritional status in children with phenylketonuria PKU. Methods: Anthropometry, blood micronutrients (Vit A, Vit E, Zn, Cu, Se, B12, folate), ferritin, haemoglobin and venous phenylalanine concentrations were retrieved from the regular annual nutritional reviews of people with PKU. Results: Cross-sectional (CS) data from the most recent annual nutritional review was available for 84 participants (13.8±7.0 y; 55% boys). For 78 patients a total of 578 visits (median visits per patient 7.5; IQR: 5 times) were available for the follow up (FU) analysis. 10.4% were obese (BMI z-score 2), 3.9% were thin (BMI z-score 2) and none was short based on the CS data. In girls there was a positive correlation between BMI z-score (r = 0.49; p = 0.005) with age and they had significantly high BMI z-scores (0.84±1.03; < 0.001). 38.4% and 42.7% of the participants had low plasma Zn and Se. B12 was below the reference intervals (RI) for 5 individuals, vitamin E and Cu for 4. 39%, 19.3% and 13% had plasma folate, red cell folate and plasma B12 concentrations respectively above the upper limit of the RI. Several patients with Zn or Se concentrations below the RI had plasma or red cell folate levels above the upper level of the RI. Based on the FU analysis subjects with good PKU control had more micronutrients with supranormal concentrations above the upper limit of the RI. On the contrary those with poor PKU control were more likely to have suboptimal Zn and Se concentrations. The proportion of those with suboptimal micronutrient concentrations did not increase with age. Conclusion: BMI z-scores were raised in girls with PKU and correlated with age in this contemporary cohort of PKU patients The origins of low Zn and Se remain unknown. “Overdosing” of other micronutrients may also occur in compliant patients and clinical staff should be aware of this. Disclosure of Interest: None Declared.
227 PP225-MON Outstanding abstract 1,25(OH)2-VITAMIN D3 ENHANCES THE STIMULATING EFFECT OF LEUCINE AND INSULIN ON PROTEIN SYNTHESIS RATE IN C2C12 SKELETAL MYOTUBES J. Salles1 , A. Chanet1 , C. Giraudet1 , V. Patrac1 , M. Jourdan2 , Y. Luiking2 , S. Verlaan2 , Y. Boirie1 , S. Walrand1 . 1 UNH, UMR 1019 INRA-UdA, INRA, Clermont-Ferrand, France; 2 Nutricia Advanced Medical Nutrition, Danone Research, Wageningen, Netherlands Rationale: Vitamin D deficiency is an increasingly described phenomenon worldwide, with potential impacts on health. In recent years, there has been a growing body of evidence suggesting an effect of vitamin D on muscle mass, morphology and function, especially in older people. The aim was to investigate the combined effect of 1,25(OH)2 -vitamin D3 (1,25OHD) with anabolic factors, insulin and leucine (Leu), on protein fractional synthesis rate (FSR) and regulation in the mouse C2C12 myotube cell line as an in vitro model for skeletal muscle. Methods: After differentiation, myotubes were cultured in 1,25OHD solutions at 0, 1, or 10nM for 72 h. Cells were then treated for 30 min by L-[1-13 C]valine in presence or not of Leu (5mM) and insulin (100nM), and FSR was determined by measuring tracer enrichments in free amino acids and proteins. Protein expression and phosphorylation state of insulin receptor (IR), Akt, mTOR, S6kinase, S6 and 4EBP1 were measured by western blot. ANOVA was used for statistical analysis. Results: When combined with 1,25OHD, the stimulation of protein FSR by Leu and insulin was dose-dependently significantly further increased by 9.8% at 1nM and by 14.3% at 10nM of 1,25OHD (p < 0.05). Akt/mTORdependent pathway was activated by Leu and insulin and this was further significantly increased by 1,25OHD (p < 0.05). Conclusion: 1,25OHD sensitizes the Akt/mTOR-dependant pathway to the stimulating effect of insulin and Leu resulting in a further activation of protein synthesis in C2C12 myotubes. Therefore, 1,25OHD potentiates the effect of insulin and Leu on skeletal muscle anabolism. Disclosure of Interest: J. Salles: None Declared, A. Chanet: None Declared, C. Giraudet: None Declared, V. Patrac: None Declared, M. Jourdan Other: Marion Jourdan is employee of Danone Research, Centre for Specialised Nutrition, Y. Luiking Other: Yvette Luiking is employee of Danone Research, Centre for Specialised Nutrition, S. Verlaan Other: Sjors Verlaan is employee of Danone Research, Centre for Specialised Nutrition, Y. Boirie: None Declared, S. Walrand: None Declared.
PP226-MON Outstanding abstract MICROGEL FORMATION OF WHEY PROTEIN REDUCES ITS INSULINOGENIC INDEX WITHOUT MODIFYING GLYCEMIC RESPONSE IN HEALTHY MEN E.B. Pouteau1 , L. Bovetto2 , G. Schlup-ollivier3 , D. Grathwohl4 , M. Beaumont4 , C. Mac´ e5 . 1 Nestl´ e Research Santiago, Maip´ u, Chile; 2 Food Science and Technology, 3 Food/Consumer Interaction, 4 BioAnalytical Science, 5 Nutrition and Health, Nestl´ e Research Centre, Lausanne, Switzerland Rationale: Chronically increased insulin demand may result in pancreatic beta cell failure, impaired glucose
228 tolerance and diabetes. Whey protein is particularly insulinogenic. The aim of this trial was to test 3 processed whey proteins (Intact vs Hydrolyzed vs Microgel) in a meal on insulin, glucagon and glycemic responses in men. Methods: In a cross-over, randomized, double blinded trial, 23 healthy adult men ingested 4 high-protein meals (30% energy) separated by a week. The proteins were the whey protein as isolate (WPI), hydrolysate (WPH) and microgel (WPM) and as reference, casein (CAS). Blood was collected after ingestion. Statistical pair-wise comparisons were used. Results: The areas under the curve (AUCs) of glycemia were similar between meals. The insulinogenic indexes were 3.7±0.5, 2.6±0.4, 2.3±0.2 and 1.9±0.2 (Mean±SE) after WPH, WPI, CAS and WPM meal ingestion, respectively (P < 0.04 between WPH and other proteins, otherwise NS). Insulin peak concentration (Cmax) after WPM meal (573±47 pmol·L 1 ) was similar than after CAS meal and lower than after WPH and WPI meals (745 780 pmol·L 1 , P < 0.004). Glucagonemia of WPM and CAS were lower than that of WPH and WPI (P < 0.05). WPH and WPI induced highest GLP-1. Amino acidemia (AA) after WPH and WPI meals was higher than after CAS meal. WPM meal induced equaled AA Cmax than WPI meal but delayed by 30 min. Total AA, essential AA, branchedchain AA and leucine showed lowest values 30 min and highest values 120 min after WPM meal intake. Conclusion: WPM meal reduces acutely insulinemia and glucagonemia compared to WPH and WPI meals, while showing same glycemia in healthy men. WPM meal shows a delayed AA peak, which might explain the reduced hormonal responses. Forming microgels confers new biological functionalities to the whey protein with potential long-term health benefits. Disclosure of Interest: None Declared.
PP227-MON Outstanding abstract PRESENCE OF NON-PATHOLOGICAL LOW GRADE INFLAMMATION REDUCES PHYSICAL PERFORMANCES IN ELDERLIES WITHOUT ALTERING PROTEIN METABOLISM RESPONSE TO FOOD INTAKE C. Buffi` ere1 , I. Savary-Auzeloux1 , M. Duclos2 , C. Mign´ e1 , 3 2 1 1 emond , D. Dardevet . S. Hercberg , N. Cano , D. R´ 1 Nutrition Humaine, INRA, CEYRAT, 2 Nutrition Humaine, CHRU, Clermont-Ferrand, 3 Unit´ e de Recherche en Epid´ emiologie Nutritionnelle, Inra/CNAM/Universit´ e Paris, Paris, France Rationale: Increased CRP levels have been correlated to sarcopenia in elderly people. On the other hand, in rodents, low grade inflammation (LGI) has been shown to be responsible of an anabolic resistance of muscle protein metabolism to food intake. However, it is not known if the presence of a chronic LGI without pathologies in aged volunteers alters protein metabolism response at the postprandial state (PP) and results in decreased fat free mass and muscle function. Methods: Elderly healthy male volunteers (69 yo) presenting no (CRP = 0.7±0.1 mg/ml) or a chronic LGI (CRP = 2.8±0.3) for 8 weeks were infused with 13 Cleucine at the post absorptive state (PA) and at the PP state following ingestion of sequential test meals. Whole body
Poster presentations protein and albumin synthesis, proteolysis and amino acid splanchnic extraction were measured as well as muscle power, strength and physical performances (VO2 max). Results: No difference in BMI, total fat and fat free mass was recorded. Whole body leucine flux, protein synthesis (PA: 1.72±0.21 vs 1.73±0.18; PP: 1.56±0.18 vs 1.66±0.17 in T and LGI, respectively) proteolysis, leucine splanchnic extraction (19% vs 17%) or albumin synthesis were not altered by the presence of LGI at both the PA or the PP states. However, trail of strength showed a decrease of total power developed, VO2 max and the duration of the test by 20%, 23% and 25% respectively. Leg muscle strength was decreased by 24% (P < 0.1). Conclusion: In healthy elderly volunteers, the presence of chronic LGI was associated with decreased physical performances without changes in total fat free mass or alteration of whole body protein metabolism in response to food intake. It may be hypothesized that higher inflammatory states are required to alter significantly protein metabolism and muscle mass but are nevertheless sufficient to decrease physical performances. Disclosure of Interest: None Declared.
PP228-MON Outstanding abstract NUTRITION SUPPORT DECREASES RISK OF PROTEIN CATABOLISM IN PATIENTS UNDERGOING BONE MARROW TRANSPLANTATION V. Matushevskaya1 , D. Fedorenko1 , V. Melnichenko1 , G. Tikhova2 . 1 Pirogov National Medical Surgical Center, 2 Peoples Friendship University of Russia Faculty of Medical Retraining, Moscow, Russian Federation Rationale: Establishing objective patient-focused goals of nutritional therapy is worthwhile to provide adequate and easy-to-assess nutritional support (NS). We aimed to test effect of 100% covering of total energy expenditure (TEE) on severity of catabolism in bone marrow transplantation (BMT) patients at different time-points of treatment before and after BMT. Methods: Autoimmune (n = 129) and oncohematologic (n = 82) patients underwent BMT: mean age 34.2±11.4 years, male/female 96/115. Patients were examined at 4 specific time-points during treatment. The degree of catabolism was defined by estimating nitrogen balance; TEE was calculated from actual body weight according to Harris Benedict equation including factors of correction. Results: In autoimmune diseases group the rate of noncatabolic patients was significantly higher at energy intake equaled 100% TEE or more comparing with those who received less than 100% TEE: before BMT RR = 2.82 (1.71; 4.64), after BMT D+7 RR = 8.03 (0.87; 74.75) and D+14 RR = 2.06 (0.83; 5.13). But at BMT time-point no association between rate of catabolism and energy intake in percents of TEE was found: RR = 1.38 (0.32; 5.96). The same relationship was found in oncohematologic patients group: before BMT RR = 2.17 (1.32; 3.86), after BMT D+7 RR = 7.38 (2.45; 22.21) and D+14 RR = 7.67 (2.77; 21.23), but at BMT all patients were severely catabolic. Conclusion: At BMT time-point NS doesn’t control severity of catabolism in BMT patients as successfully as it does at the other phases of treatment. Energy intake equaled 100% TEE or more substantially decreases
PP224-MON NUTRITIONAL STATUS IN CHILDREN WITH PHENYLKETONURIA H.N. Choong1 , B. Cochrane2 , J. Jones3 , P. Robinson4 , B. Schwahn4 , K. Gerasimidis1 . 1 Human Nutrition, University of Glasgow, 2 Department of Dietetics, 3 Department of Endocrinology, 4 Department of Inherited Disorders of Metabolism, NHS Greater Glasgow & Clyde, Glasgow, United Kingdom Rationale: There is a scarcity of studies which characterise and examine predictors of nutritional status in children with phenylketonuria PKU. Methods: Anthropometry, blood micronutrients (Vit A, Vit E, Zn, Cu, Se, B12, folate), ferritin, haemoglobin and venous phenylalanine concentrations were retrieved from the regular annual nutritional reviews of people with PKU. Results: Cross-sectional (CS) data from the most recent annual nutritional review was available for 84 participants (13.8±7.0 y; 55% boys). For 78 patients a total of 578 visits (median visits per patient 7.5; IQR: 5 times) were available for the follow up (FU) analysis. 10.4% were obese (BMI z-score 2), 3.9% were thin (BMI z-score 2) and none was short based on the CS data. In girls there was a positive correlation between BMI z-score (r = 0.49; p = 0.005) with age and they had significantly high BMI z-scores (0.84±1.03; < 0.001). 38.4% and 42.7% of the participants had low plasma Zn and Se. B12 was below the reference intervals (RI) for 5 individuals, vitamin E and Cu for 4. 39%, 19.3% and 13% had plasma folate, red cell folate and plasma B12 concentrations respectively above the upper limit of the RI. Several patients with Zn or Se concentrations below the RI had plasma or red cell folate levels above the upper level of the RI. Based on the FU analysis subjects with good PKU control had more micronutrients with supranormal concentrations above the upper limit of the RI. On the contrary those with poor PKU control were more likely to have suboptimal Zn and Se concentrations. The proportion of those with suboptimal micronutrient concentrations did not increase with age. Conclusion: BMI z-scores were raised in girls with PKU and correlated with age in this contemporary cohort of PKU patients The origins of low Zn and Se remain unknown. “Overdosing” of other micronutrients may also occur in compliant patients and clinical staff should be aware of this. Disclosure of Interest: None Declared.
227 PP225-MON Outstanding abstract 1,25(OH)2-VITAMIN D3 ENHANCES THE STIMULATING EFFECT OF LEUCINE AND INSULIN ON PROTEIN SYNTHESIS RATE IN C2C12 SKELETAL MYOTUBES J. Salles1 , A. Chanet1 , C. Giraudet1 , V. Patrac1 , M. Jourdan2 , Y. Luiking2 , S. Verlaan2 , Y. Boirie1 , S. Walrand1 . 1 UNH, UMR 1019 INRA-UdA, INRA, Clermont-Ferrand, France; 2 Nutricia Advanced Medical Nutrition, Danone Research, Wageningen, Netherlands Rationale: Vitamin D deficiency is an increasingly described phenomenon worldwide, with potential impacts on health. In recent years, there has been a growing body of evidence suggesting an effect of vitamin D on muscle mass, morphology and function, especially in older people. The aim was to investigate the combined effect of 1,25(OH)2 -vitamin D3 (1,25OHD) with anabolic factors, insulin and leucine (Leu), on protein fractional synthesis rate (FSR) and regulation in the mouse C2C12 myotube cell line as an in vitro model for skeletal muscle. Methods: After differentiation, myotubes were cultured in 1,25OHD solutions at 0, 1, or 10nM for 72 h. Cells were then treated for 30 min by L-[1-13 C]valine in presence or not of Leu (5mM) and insulin (100nM), and FSR was determined by measuring tracer enrichments in free amino acids and proteins. Protein expression and phosphorylation state of insulin receptor (IR), Akt, mTOR, S6kinase, S6 and 4EBP1 were measured by western blot. ANOVA was used for statistical analysis. Results: When combined with 1,25OHD, the stimulation of protein FSR by Leu and insulin was dose-dependently significantly further increased by 9.8% at 1nM and by 14.3% at 10nM of 1,25OHD (p < 0.05). Akt/mTORdependent pathway was activated by Leu and insulin and this was further significantly increased by 1,25OHD (p < 0.05). Conclusion: 1,25OHD sensitizes the Akt/mTOR-dependant pathway to the stimulating effect of insulin and Leu resulting in a further activation of protein synthesis in C2C12 myotubes. Therefore, 1,25OHD potentiates the effect of insulin and Leu on skeletal muscle anabolism. Disclosure of Interest: J. Salles: None Declared, A. Chanet: None Declared, C. Giraudet: None Declared, V. Patrac: None Declared, M. Jourdan Other: Marion Jourdan is employee of Danone Research, Centre for Specialised Nutrition, Y. Luiking Other: Yvette Luiking is employee of Danone Research, Centre for Specialised Nutrition, S. Verlaan Other: Sjors Verlaan is employee of Danone Research, Centre for Specialised Nutrition, Y. Boirie: None Declared, S. Walrand: None Declared.
PP226-MON Outstanding abstract MICROGEL FORMATION OF WHEY PROTEIN REDUCES ITS INSULINOGENIC INDEX WITHOUT MODIFYING GLYCEMIC RESPONSE IN HEALTHY MEN E.B. Pouteau1 , L. Bovetto2 , G. Schlup-ollivier3 , D. Grathwohl4 , M. Beaumont4 , C. Mac´ e5 . 1 Nestl´ e Research Santiago, Maip´ u, Chile; 2 Food Science and Technology, 3 Food/Consumer Interaction, 4 BioAnalytical Science, 5 Nutrition and Health, Nestl´ e Research Centre, Lausanne, Switzerland Rationale: Chronically increased insulin demand may result in pancreatic beta cell failure, impaired glucose
228 tolerance and diabetes. Whey protein is particularly insulinogenic. The aim of this trial was to test 3 processed whey proteins (Intact vs Hydrolyzed vs Microgel) in a meal on insulin, glucagon and glycemic responses in men. Methods: In a cross-over, randomized, double blinded trial, 23 healthy adult men ingested 4 high-protein meals (30% energy) separated by a week. The proteins were the whey protein as isolate (WPI), hydrolysate (WPH) and microgel (WPM) and as reference, casein (CAS). Blood was collected after ingestion. Statistical pair-wise comparisons were used. Results: The areas under the curve (AUCs) of glycemia were similar between meals. The insulinogenic indexes were 3.7±0.5, 2.6±0.4, 2.3±0.2 and 1.9±0.2 (Mean±SE) after WPH, WPI, CAS and WPM meal ingestion, respectively (P < 0.04 between WPH and other proteins, otherwise NS). Insulin peak concentration (Cmax) after WPM meal (573±47 pmol·L 1 ) was similar than after CAS meal and lower than after WPH and WPI meals (745 780 pmol·L 1 , P < 0.004). Glucagonemia of WPM and CAS were lower than that of WPH and WPI (P < 0.05). WPH and WPI induced highest GLP-1. Amino acidemia (AA) after WPH and WPI meals was higher than after CAS meal. WPM meal induced equaled AA Cmax than WPI meal but delayed by 30 min. Total AA, essential AA, branchedchain AA and leucine showed lowest values 30 min and highest values 120 min after WPM meal intake. Conclusion: WPM meal reduces acutely insulinemia and glucagonemia compared to WPH and WPI meals, while showing same glycemia in healthy men. WPM meal shows a delayed AA peak, which might explain the reduced hormonal responses. Forming microgels confers new biological functionalities to the whey protein with potential long-term health benefits. Disclosure of Interest: None Declared.
PP227-MON Outstanding abstract PRESENCE OF NON-PATHOLOGICAL LOW GRADE INFLAMMATION REDUCES PHYSICAL PERFORMANCES IN ELDERLIES WITHOUT ALTERING PROTEIN METABOLISM RESPONSE TO FOOD INTAKE C. Buffi` ere1 , I. Savary-Auzeloux1 , M. Duclos2 , C. Mign´ e1 , 3 2 1 1 emond , D. Dardevet . S. Hercberg , N. Cano , D. R´ 1 Nutrition Humaine, INRA, CEYRAT, 2 Nutrition Humaine, CHRU, Clermont-Ferrand, 3 Unit´ e de Recherche en Epid´ emiologie Nutritionnelle, Inra/CNAM/Universit´ e Paris, Paris, France Rationale: Increased CRP levels have been correlated to sarcopenia in elderly people. On the other hand, in rodents, low grade inflammation (LGI) has been shown to be responsible of an anabolic resistance of muscle protein metabolism to food intake. However, it is not known if the presence of a chronic LGI without pathologies in aged volunteers alters protein metabolism response at the postprandial state (PP) and results in decreased fat free mass and muscle function. Methods: Elderly healthy male volunteers (69 yo) presenting no (CRP = 0.7±0.1 mg/ml) or a chronic LGI (CRP = 2.8±0.3) for 8 weeks were infused with 13 Cleucine at the post absorptive state (PA) and at the PP state following ingestion of sequential test meals. Whole body
Poster presentations protein and albumin synthesis, proteolysis and amino acid splanchnic extraction were measured as well as muscle power, strength and physical performances (VO2 max). Results: No difference in BMI, total fat and fat free mass was recorded. Whole body leucine flux, protein synthesis (PA: 1.72±0.21 vs 1.73±0.18; PP: 1.56±0.18 vs 1.66±0.17 in T and LGI, respectively) proteolysis, leucine splanchnic extraction (19% vs 17%) or albumin synthesis were not altered by the presence of LGI at both the PA or the PP states. However, trail of strength showed a decrease of total power developed, VO2 max and the duration of the test by 20%, 23% and 25% respectively. Leg muscle strength was decreased by 24% (P < 0.1). Conclusion: In healthy elderly volunteers, the presence of chronic LGI was associated with decreased physical performances without changes in total fat free mass or alteration of whole body protein metabolism in response to food intake. It may be hypothesized that higher inflammatory states are required to alter significantly protein metabolism and muscle mass but are nevertheless sufficient to decrease physical performances. Disclosure of Interest: None Declared.
PP228-MON Outstanding abstract NUTRITION SUPPORT DECREASES RISK OF PROTEIN CATABOLISM IN PATIENTS UNDERGOING BONE MARROW TRANSPLANTATION V. Matushevskaya1 , D. Fedorenko1 , V. Melnichenko1 , G. Tikhova2 . 1 Pirogov National Medical Surgical Center, 2 Peoples Friendship University of Russia Faculty of Medical Retraining, Moscow, Russian Federation Rationale: Establishing objective patient-focused goals of nutritional therapy is worthwhile to provide adequate and easy-to-assess nutritional support (NS). We aimed to test effect of 100% covering of total energy expenditure (TEE) on severity of catabolism in bone marrow transplantation (BMT) patients at different time-points of treatment before and after BMT. Methods: Autoimmune (n = 129) and oncohematologic (n = 82) patients underwent BMT: mean age 34.2±11.4 years, male/female 96/115. Patients were examined at 4 specific time-points during treatment. The degree of catabolism was defined by estimating nitrogen balance; TEE was calculated from actual body weight according to Harris Benedict equation including factors of correction. Results: In autoimmune diseases group the rate of noncatabolic patients was significantly higher at energy intake equaled 100% TEE or more comparing with those who received less than 100% TEE: before BMT RR = 2.82 (1.71; 4.64), after BMT D+7 RR = 8.03 (0.87; 74.75) and D+14 RR = 2.06 (0.83; 5.13). But at BMT time-point no association between rate of catabolism and energy intake in percents of TEE was found: RR = 1.38 (0.32; 5.96). The same relationship was found in oncohematologic patients group: before BMT RR = 2.17 (1.32; 3.86), after BMT D+7 RR = 7.38 (2.45; 22.21) and D+14 RR = 7.67 (2.77; 21.23), but at BMT all patients were severely catabolic. Conclusion: At BMT time-point NS doesn’t control severity of catabolism in BMT patients as successfully as it does at the other phases of treatment. Energy intake equaled 100% TEE or more substantially decreases