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Caloric restriction increases muscle and liver mitochondrial oxidative capacity in young but not in old rats
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CELL BIOLOGY, NUTRIENTS AND GENES
with LCT n-3, in relation to control (med=199.5) and the other groups without LCTn-3 (for mixtue with MCT). Conclusions: Our findings shows that LCTn-3 inhibit the expression of HLA-DR on in-activation M O surface, principally when added to MCT, supporting previous studies that shows a protective effect of LCTn-3 in the treatment of inflammatory diseases, were immune cells activation can enhance the inflammation intensity.
159-P. EFFECTS OF IMMUNE-ENHANCING ENTERAL FORMULA ON LPS-INDUCED ELEVATION OF PLASMA IL-6 AND TNF-ALPHA IN MALNOURISHED MICE K.t, S. Okada’, H. Ohashi’, K. Yokotani’, S. Ogoshi3 ‘Pharmacology, Kochi Medical School, Nankoku, 2Pharmaceutical Company, Ajinomoto Co., Inc, Tokyo, 3 Vice-President, Kochi Medical School, Nankoku, Japan Rationale: Protein malnutrition is a major issue for prognosis of hospitaliced patients, since it impairs their immune functions thereby increasing a possibility of opportunistic infections and septic shock. Nutrients containing glutamine, xginine, omega-3 fatty acids and nucleotides have an immuneenhancing effect for severe illness, bun, trauma, and surgical stress. This study was designed to examined the effect of enteral formulas enriched with immunonutrients on immune nsponses to inflammatory stress in malnourished mice. Method: Mice (5-wk of age) were divided into fom groups [G-l, nomal diet (25.4% of protein) (n=ll); G-2, low protein diet (LPD)(S%) (n=12); G-3, LPD+immunonutrition (IMPACT) (n=l 1); G-4, LPD+standard diet (MEDI-F) (n=12)]. IMPACT and MEDI-F were applied for the last 3 days. On the last day, LPS (50 mg/mouse, i.p.) was administered in each group and plasma IL-6 and TNF-alpha wele measured 1.5 hs after LPS administration. Results: (1) The LPS-induced elevations of plasma IL-6 (lOSf13 rig/ml) and TNF-alpha (14f4 rig/ml) in G-2 were significantly (piO.01) higher than those in G-l (IL-6, 29f7 rig/ml: TNF-alpha 0.3fO.l rig/ml). (2) In the groups treated with LPD (G-2,3,4), the LPS-induced elevation of plasma IL-6 was significantly attenuated by IMPACT (72f9 rig/ml, piO.05) (G3) and MEDI-F (62f5 rig/ml, piO.01) (G-4), however the LPS-induced elevation of plasma TNF-alpha was not influenced. Conclusions: In malnourished mice, the LPS-induced elevation of plasma IL-6, but not TNF-alpha, was effectively attenuated by immunonuhition. From these results, it seems likely that immunonutrition is effective for treatment of extreme inflammatory responses.
160-P. CALORIC RESTRICTION INCREASES MUSCLE AND LIVER MITOCHONDRIAL OXIDATIVE CAPACITY IN YOUNG BUT NOT IN OLD RATS R. Barazzoni ‘, M. Zanetti’, L. Visintin’, G. Biolo’ , M. Stebel’, L. Cattin ‘, G. Guamieri ’ ‘Dept of Clinical Morphological Technological Sciences Clinica Medica, ‘CSPA-Animal Facility, University of Trieste, Trieste, Italy Rationale: Mitochondria play a key role in tissue energy production. Impalled mitochon&ial oxidative capacity may contribute to aging process. Caloric restriction in adult age is hypothesized to improve mitochon&ial function. Reduced caloric intake can however be detrimental in aging. We hypothesized that moderate CR increases tissue mitochondrial oxidative capacity in young but not in old rats Method: Activity of cytochrome c oxidase (COX, respiratory chain enzyme) was measured in gastrocnemius muscle and liver in adult (6-mo) and old (24-mo-old) male rats. In each age group, 6 rats ate ad lib a balanced chow diet (CON) and 6 rats had 25% reduced amounts of same diet (CR) for three weeks Results: Body weight was comparable in young (392fS g) and old (404f7) CON, and CR rats lost similar weight (-7% body weight) in both age groups. COX activity was comparable in young and old CON rats in both gastrocnemius (Y: 158f29, 0: 153f31 wmol/min.g protein) and liver (Y: 459f31, 0: 404f33) (P>O.6). CR resulted in higher COX enzyme activity in gastrocnemius (+60%) and liver tissue (+30%) in young animals (both PiO.05
young CR vs young CON). In contrast, COX activity was unchanged in old CR compared to old CON animals in both tissues (P>O.6) Conclusions: Moderate caloric restriction enhances mitochondrial oxidative capacity in adult rat muscle and liver. These changes may favom subs&ate utilization over storage during reduced nutrient intake and contribute to beneficial metabolic effects of caloric restriction. Stimulation of mitochondrial function by caloric restriction is abolished with aging. This novel age-related mitochon&ial defect may play a role in metabolic alterations and may alter lean tissue response to nutrient restriction in old age
161-P. ENDOTOXIN-INDUCED PROTEIN CATABOLISM IN MAN IS CLOSELY RELATED TO THE PROINFLAMMATORY CYTOKINE RESPONSE A.S.A. Khan t , M. Soop ‘, 0. Rooyackers 3, K. Kaushal ’, E.A. Gxdener ‘, K.L. Tieszen’, 0. Ljungqvist’, J.P. New4, J.M. Gibson4, G.L. Carlson’ ’1, University of Manchester; Hope hospital, Manchester, United Kingdom, 22, Ersta Hospital, Karolinska Institutet, 33, Huddinge University Hospital, Stockholm, Sweden, 41, Hope Hospital, Saljord, ‘4, Injury Research Group, Hope Hospital, Manchester, United Kingdom Rationale: To study whole body protein metabolism in man during experimental endotoxaemia. Method: Six healthy male subjects were studied twice in the post-absorptive state, 14-21 days apxt, receiving either IV endotoxin (LPS, 4 rig/kg) or sterile 0.9% saline at 0 min. Primed-continuous IV infusions of 2H5phenylalanine, 2H2-tyrosine, & 2HCtyrosine (prime only) were commenced at -150 min. Arterialized venous blood samples were taken every 10 min, for 6 separate 30 min periods, from -30 min to +630 min. Samples were analysed for isotopic enrichment by GC-MS; and for TNF-a and IL-6 by immune-assay. Results are presented as mean difference (LPS - Saline) in xea under curve [95% confidence interval]. Results: LPS significantly increased protein bleakdown (0.95 [0.61 - 1.291 mg/kg/h, p=O.OOl) and protein synthesis rates (0.84 [0.52 - 1.161 mg/kg/h, p=O.OOl), in compxison with saline. Net protein balance was negative in both study arms but more so with LPS (0.11 [O.OS- 0.141 mg/kg/h, piO.001). LPS-induced changes in protein breakdown and synthesis cointided with peak plasma IL-6 and TNF-a concentrations at 120 min. Conclusions: Acute endotoxaemia is a valid model for studying stressinduced protein metabolism in man because it significantly increases whole body protein breakdown, protein synthesis, and net protein loss in healthy subjects. The time course of this response suggests a mechanistic role for proinflammtory cytokines.
162-P. PREVENTIVE EFFECT OF N-ACETYL-GLUTAMINE (NAQ) VS GLUTAMINE (Q) ON INTESTINAL DYSFUNCTION INDUCED BY PROTEIN-ENERGY MALNUTRITION (PEM) IN PIGS M. Manzano’, R. Rueda’, J.H. Baxter’, J.M. Lowz-Pe&osa’ ‘International RD, RPD, ABBOTTLaboratoties, Granada, Spain, ‘Strategic Research, RPD, ABBOTTLaboratoties, Columbus-OH, United States Rationale: The addition of glutamine to TEN formulations improves intestinal mucosal integrity and immune function. However, free glutamine is not included in liquid formulas due to its long-telm-instability. The goal of this study was to evaluate the preventive effect of feeding a diet supplemented with Q or NAQ, a liquid stable source of Q, on gut histologic and immunological changes induced by PEM in pigs Method: Pigs (5 wk old) were assigned to one of two groups. Healthy group (n=6) was fed a liquid formula for 30 d. Malnourished group (n=lS) received only 20% of the food intake recorded in control group and was divided into 3 subgroups (n=6) which daily received a supplement of caseinate, Q or NAQ, respectively, during the malnutrition period (30 d). The intestinal immunological response was evaluated by measuring total cell number, and the expression of different cell surface antigens (CD3, CD4, CDS and CD21) in Peyer’s patches lymphocytes (PPL). Small intestinal samples were examined by electron transmission microscopy.
CELL BIOLOGY, NUTRIENTS AND GENES
with LCT n-3, in relation to control (med=199.5) and the other groups without LCTn-3 (for mixtue with MCT). Conclusions: Our findings shows that LCTn-3 inhibit the expression of HLA-DR on in-activation M O surface, principally when added to MCT, supporting previous studies that shows a protective effect of LCTn-3 in the treatment of inflammatory diseases, were immune cells activation can enhance the inflammation intensity.
159-P. EFFECTS OF IMMUNE-ENHANCING ENTERAL FORMULA ON LPS-INDUCED ELEVATION OF PLASMA IL-6 AND TNF-ALPHA IN MALNOURISHED MICE K.t, S. Okada’, H. Ohashi’, K. Yokotani’, S. Ogoshi3 ‘Pharmacology, Kochi Medical School, Nankoku, 2Pharmaceutical Company, Ajinomoto Co., Inc, Tokyo, 3 Vice-President, Kochi Medical School, Nankoku, Japan Rationale: Protein malnutrition is a major issue for prognosis of hospitaliced patients, since it impairs their immune functions thereby increasing a possibility of opportunistic infections and septic shock. Nutrients containing glutamine, xginine, omega-3 fatty acids and nucleotides have an immuneenhancing effect for severe illness, bun, trauma, and surgical stress. This study was designed to examined the effect of enteral formulas enriched with immunonutrients on immune nsponses to inflammatory stress in malnourished mice. Method: Mice (5-wk of age) were divided into fom groups [G-l, nomal diet (25.4% of protein) (n=ll); G-2, low protein diet (LPD)(S%) (n=12); G-3, LPD+immunonutrition (IMPACT) (n=l 1); G-4, LPD+standard diet (MEDI-F) (n=12)]. IMPACT and MEDI-F were applied for the last 3 days. On the last day, LPS (50 mg/mouse, i.p.) was administered in each group and plasma IL-6 and TNF-alpha wele measured 1.5 hs after LPS administration. Results: (1) The LPS-induced elevations of plasma IL-6 (lOSf13 rig/ml) and TNF-alpha (14f4 rig/ml) in G-2 were significantly (piO.01) higher than those in G-l (IL-6, 29f7 rig/ml: TNF-alpha 0.3fO.l rig/ml). (2) In the groups treated with LPD (G-2,3,4), the LPS-induced elevation of plasma IL-6 was significantly attenuated by IMPACT (72f9 rig/ml, piO.05) (G3) and MEDI-F (62f5 rig/ml, piO.01) (G-4), however the LPS-induced elevation of plasma TNF-alpha was not influenced. Conclusions: In malnourished mice, the LPS-induced elevation of plasma IL-6, but not TNF-alpha, was effectively attenuated by immunonuhition. From these results, it seems likely that immunonutrition is effective for treatment of extreme inflammatory responses.
160-P. CALORIC RESTRICTION INCREASES MUSCLE AND LIVER MITOCHONDRIAL OXIDATIVE CAPACITY IN YOUNG BUT NOT IN OLD RATS R. Barazzoni ‘, M. Zanetti’, L. Visintin’, G. Biolo’ , M. Stebel’, L. Cattin ‘, G. Guamieri ’ ‘Dept of Clinical Morphological Technological Sciences Clinica Medica, ‘CSPA-Animal Facility, University of Trieste, Trieste, Italy Rationale: Mitochondria play a key role in tissue energy production. Impalled mitochon&ial oxidative capacity may contribute to aging process. Caloric restriction in adult age is hypothesized to improve mitochon&ial function. Reduced caloric intake can however be detrimental in aging. We hypothesized that moderate CR increases tissue mitochondrial oxidative capacity in young but not in old rats Method: Activity of cytochrome c oxidase (COX, respiratory chain enzyme) was measured in gastrocnemius muscle and liver in adult (6-mo) and old (24-mo-old) male rats. In each age group, 6 rats ate ad lib a balanced chow diet (CON) and 6 rats had 25% reduced amounts of same diet (CR) for three weeks Results: Body weight was comparable in young (392fS g) and old (404f7) CON, and CR rats lost similar weight (-7% body weight) in both age groups. COX activity was comparable in young and old CON rats in both gastrocnemius (Y: 158f29, 0: 153f31 wmol/min.g protein) and liver (Y: 459f31, 0: 404f33) (P>O.6). CR resulted in higher COX enzyme activity in gastrocnemius (+60%) and liver tissue (+30%) in young animals (both PiO.05
young CR vs young CON). In contrast, COX activity was unchanged in old CR compared to old CON animals in both tissues (P>O.6) Conclusions: Moderate caloric restriction enhances mitochondrial oxidative capacity in adult rat muscle and liver. These changes may favom subs&ate utilization over storage during reduced nutrient intake and contribute to beneficial metabolic effects of caloric restriction. Stimulation of mitochondrial function by caloric restriction is abolished with aging. This novel age-related mitochon&ial defect may play a role in metabolic alterations and may alter lean tissue response to nutrient restriction in old age
161-P. ENDOTOXIN-INDUCED PROTEIN CATABOLISM IN MAN IS CLOSELY RELATED TO THE PROINFLAMMATORY CYTOKINE RESPONSE A.S.A. Khan t , M. Soop ‘, 0. Rooyackers 3, K. Kaushal ’, E.A. Gxdener ‘, K.L. Tieszen’, 0. Ljungqvist’, J.P. New4, J.M. Gibson4, G.L. Carlson’ ’1, University of Manchester; Hope hospital, Manchester, United Kingdom, 22, Ersta Hospital, Karolinska Institutet, 33, Huddinge University Hospital, Stockholm, Sweden, 41, Hope Hospital, Saljord, ‘4, Injury Research Group, Hope Hospital, Manchester, United Kingdom Rationale: To study whole body protein metabolism in man during experimental endotoxaemia. Method: Six healthy male subjects were studied twice in the post-absorptive state, 14-21 days apxt, receiving either IV endotoxin (LPS, 4 rig/kg) or sterile 0.9% saline at 0 min. Primed-continuous IV infusions of 2H5phenylalanine, 2H2-tyrosine, & 2HCtyrosine (prime only) were commenced at -150 min. Arterialized venous blood samples were taken every 10 min, for 6 separate 30 min periods, from -30 min to +630 min. Samples were analysed for isotopic enrichment by GC-MS; and for TNF-a and IL-6 by immune-assay. Results are presented as mean difference (LPS - Saline) in xea under curve [95% confidence interval]. Results: LPS significantly increased protein bleakdown (0.95 [0.61 - 1.291 mg/kg/h, p=O.OOl) and protein synthesis rates (0.84 [0.52 - 1.161 mg/kg/h, p=O.OOl), in compxison with saline. Net protein balance was negative in both study arms but more so with LPS (0.11 [O.OS- 0.141 mg/kg/h, piO.001). LPS-induced changes in protein breakdown and synthesis cointided with peak plasma IL-6 and TNF-a concentrations at 120 min. Conclusions: Acute endotoxaemia is a valid model for studying stressinduced protein metabolism in man because it significantly increases whole body protein breakdown, protein synthesis, and net protein loss in healthy subjects. The time course of this response suggests a mechanistic role for proinflammtory cytokines.
162-P. PREVENTIVE EFFECT OF N-ACETYL-GLUTAMINE (NAQ) VS GLUTAMINE (Q) ON INTESTINAL DYSFUNCTION INDUCED BY PROTEIN-ENERGY MALNUTRITION (PEM) IN PIGS M. Manzano’, R. Rueda’, J.H. Baxter’, J.M. Lowz-Pe&osa’ ‘International RD, RPD, ABBOTTLaboratoties, Granada, Spain, ‘Strategic Research, RPD, ABBOTTLaboratoties, Columbus-OH, United States Rationale: The addition of glutamine to TEN formulations improves intestinal mucosal integrity and immune function. However, free glutamine is not included in liquid formulas due to its long-telm-instability. The goal of this study was to evaluate the preventive effect of feeding a diet supplemented with Q or NAQ, a liquid stable source of Q, on gut histologic and immunological changes induced by PEM in pigs Method: Pigs (5 wk old) were assigned to one of two groups. Healthy group (n=6) was fed a liquid formula for 30 d. Malnourished group (n=lS) received only 20% of the food intake recorded in control group and was divided into 3 subgroups (n=6) which daily received a supplement of caseinate, Q or NAQ, respectively, during the malnutrition period (30 d). The intestinal immunological response was evaluated by measuring total cell number, and the expression of different cell surface antigens (CD3, CD4, CDS and CD21) in Peyer’s patches lymphocytes (PPL). Small intestinal samples were examined by electron transmission microscopy.