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O.16 Growth hormone (GH) stimulates albumin but notmuscle synthesis in HIV+ individuals
Results: Rates of duodenal mucosal protein synthesis were 2.58 _+ 0.32 (%h-I, mean _+ SD) in the normal subjects vs 2.04 -+ 0.18 in the ALD patients P < 0.003. Protein/DNA ratio was lower in the ALD (ALD vs control, 9.23 _+0.91 vs 13 + 2.2 #g/mg, P < 0.002). The protein synthetic capacity (RNA/protein) of the intestinal mucosal was higher in ALD (ALD vs control), 160 _+ 14 vs 137 _+6~g/mg, P < 0.003). There was no difference in the mean values of whole-body protein turnover between the two groups. However, in ALD patients there was a positive correlation between whole body breakdown and indices of disease severity (t = 0.88, P < 0.01) and a negative correlation with small intestinal mucosal protein synthesis (r = 0.72, P < 0.01 ). Conclusions: The rate of intestinal mucosal protein synthesis was depressed by 21% in ALD, despite a 16% increase in the protein synthetic capacity. The lean tissue wasting observed in ALD appears to extend to the gastrointestinal tract, which shows a depressed anabolic activity (despite a sufficient synthetic capacity) in proportion to whole body breakdown. The functional significance of these changes remain to be established.
O.16 Growth hormone (GH) stimulates albumin but not muscle synthesis in HIV+ individuals M. A. McNurlan ~, P. J. Garlick ~, K. DeCristofaro 2, R. A. Frost 2, C. H.
Lang 1, R. Steigbigel 2, J. Fuhrer 2 and M. C. Gelato 2 Departments of ISurgery and 2Medicine, State University of New York, Stony Brook, NY, USA. HIV infection is associated with profound metabolic abnormalities, includ-
ing loss of lean body mass. The purpose of this study was to assess the effect of growth hormone (GH) administration on the synthesis of muscle protein and albumin in HIV + individuals. GH (Serono, Norwell, MA) was given at 6mg/d for 2 weeks, with dietary advice on increasing protein intake to 20% of energy. Serum GH levels were determined prior to treatment on samples taken every 20 rain between 22:00 and 06:00. Protein synthesis was measured, in fasting subjects prior to and after GH treatment, from the incorporation of L-[2H5]phenylalanine (45 mg/kg, 10-20 atoms %) into protein of the vastus lateralis muscle (5 control, 6 HIV) and plasma albumin (5 control, 8 HIV). Plasma GH levels in the HIV group were significantly lower than controls in both peak amplitude (22.1 -+7.0 (SEM) #g L-~ vs 4.2 _+0.7, P= 0.08) and the area under the concentration-time curve (77 +_40 #g L-~ 24 h-1 vs 6.4 _+ 2.2, P = 0.04). GH increased body weight in control (2.7 _+0.5 kg) and HIV (2.1 + 0.4 kg), and increased IGF-I 3- to 4-fold. Muscle protein synthesis increased by 40 _+ 19% in controls, but decreased by 29 _+ 18% in HIV+ subjects (control vs HIV, P = 0.03). In control subjects, albumin synthesis rose from 6.5 + 0.5% d-~ to 10.1 + 2.0 (P = 0.06), as a fraction of the intravascular albumin mass (FSR), and increased from 7.5 + 0.7gd -~ to tl .0 + 1.9 (P = 0.05), as the amount of albumin synthesized each day (ASR). In HIV+ subjects albumin FSR increased from 7.8 _+0.6% d-~ to 9.3 _+0.6 (P = 0.02), and ASR increased from 10.4 _+1.0 g d-~ to 12.5 _+1.1 (P = 0.03). GH treatment for 2 weeks resulted in the stimulation of albumin synLhesis in both control and HIV subjects. Muscle synthesis was stimulated in control subjects, but not in those with HIV infection. Thus, the pathological state alters the anabolic action of GH in a tissue specific manner.
3rd S e s s i o n - P E D I A T R I C S , E N T E R A L N U T R I T I O N
O.17 Acute effect of oral glutamine on whole body leucine and glutamine metabolism in Duchenne muscular dystrophy
O.18 The risk of dyslipoproteinaemia in obese children is influenced by apolipoprotein E polymorphism
R. Hankard, D. Hammond, M. Haymond and D. Darrnaun
Girardet** **Pediatric Gastroenterology and Nutrition, Trousseau Teaching Hospital, 26 Av. du Dr. A. Netter, 75571 Paris Cedex 12, France; *Biochemistry B, Saint-Antoine Teaching Hospital, 184 rue du Faubourg St.-Antoine, 75012 Paris, France.
Nemours Children's Clinic, Jacksonville, USA. Glutamine is thought to play a key role in protein homeostasis, and muscle mass loss in Duchenne muscular dystrophy (DMD) is associated with low intramuscular glutamine concentration. Previous studies have documented a protein sparing effect of glutarnine administration in stressed patients who have low intramuscular glutamine concentration, as well as in healthy humans. To determine whether glutamine has a protein anabolic effect in DMD, six 8- to 13-year-old DMD boys received 5-h intravenous infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state, and on 2 consecutive days while drinking: a) small, frequent sips of flavoured water on one day, and b) the same drink mixed with L-glutamine (800 ~mol.Kg -1.h -1), the other day. Body leucine (Ra.~eu) and glutamine (R ag=n) rate of appearance in plasma were determined from 13C-o~-ketoisocaproate, the intracelluiar metabolite of leucine, and ~SN-glutamine enrichments in plasma. Leucine oxidation rate (OX~eu)was calculated from 13CO2 enrichment in expired air, and the non-oxidative leucine disposal (NOLD), an index of protein synthesis, was: Ra.teu OXle u, Endogenous aa,gln (EndORa,gln) was calculated assuming that 50% of enteral glutamine reaches the bloodstream. Estimates of glutamine release from protein breakdown (Bgln), and glutamine de novo synthesis (Dgln) were calculated from Ra,~eu. Results are means _+SEM, statistical tests with paired t-test. During oral glutamine administration, aa,gln doubled from 321 _ 22 to 623 _+24#moI.Kg-~.h -~, P < 0.01, but EndoRa,g~n decreased from 321 _+22 to 247 +_241~moI.Kg-~.h -~, P = 0.01, resulting from a decrease in both Bgln (91 +- 4 vs 84 -+ 5 #moI.Kg -~.h -1, P < 0.01), and Dgln (230 +_21 vs 163 + 25 #mol.Kg-~.h -1, P = 0.02). During oral glutamine administration, R~,~eodecreased by 8% from 116 -+ 5 to 107 _+ 6#mol.Kg-~.h -~ ( P < 0.01), Ox~eudecreased by 35% from 23 _+2 to 15 _+ 2#mol.Kg-~.h -1 (P < 0.01), but NOLD did not change (93 -+ 4 vs 92 _+ 5 #mol.Kg -1 .h-1 , NS). Conclusions: These data suggest that in DMD children, acute oral glutamine administration: 1) is associated with a decrease in leucine release from protein degradation and might have a protein sparing effect inhibiting whole body protein breakdown, 2) inhibits endogenous glutamine production, therefore sparing nitrogen precursors. Further studies are warranted to determine the effect of long-term glutamine administration on muscle mass and function in DMD.
G. Parlier**, G. Thomas, G. BCrezait*, J. L. Fontaine** and J. Ph.
In adults, apoliprotein (Apo) E polymorphism modulates the consequences of obesity on lipid metabolism and patients with the ~2 and ~4 alleles are at increased risk of obesity-induced dyslipidemia. The purpose of this study was to determine whether Apo E polymorphism also influences the risk of dyslipidemia in obese children. Study population: We studied 137 non-genetically-related paediatfic patients (78 girls), aged 2.2-14.4 years (mean 9.9 -+ 3.1 years), with a body mass index greater than the 97th gender- and age-specific centile and a mean excess weight-for-height of 43.7 _+17.9%. Methods: (1) The Apo E genotype was determined by studying specific restriction profiles of ADN amplified by a PCR technique involving use of a pair of probes that recognized a specific sequence of exon 4 of the Apo E gene. (2) Total cholesterol (TC), HDL-cholesterol and triglycerides (TG) were assayed in fasting plasma samples taken before initiation of dietary treatment; LDL-cholesterol (LDL-C) was calculated using Friedwald's formula. Values for TC, TG, and LDL-C were classified as abnormal if they exceeded the 95th centile of values in the general paediatric population [1]. Results: The distribution of Apo E alleles was similar to that reported in the general Caucasian population (£2 = 6.2%; £3 = 82.1%, and s4 = 11.7%). (2) Fifty-five subjects (40.7%) had hyperlipidemia: 34 subjects (25.1%) with high LDL-C levels, including 23 with no other lipid abnormality and 32 subjects (23.4%) with high TG levels, including 21 with no other lipid abnormality. (3) The ~2 allele was associated with a higher prevalence of hypertriglyceridaemia as compared with the ~3 and E4 alleles (52.9% vs 19.5%, P < 0.05) Subjects with ~4 allele were more likely to have high LDL-C levels than subjects with the ~3 and ~2 alleles (34.7% vs 13.4%, P< 0.05). Conclusions: (1) Obesity is associated with a marked increase iin the risk of dyslipidemia even in childhood. (2) This risk is influenced by Apo E polymorphism, in particular by alleles ~2 and ~4, which have different effects on lipid metabolism.
Reference: [1] The LRC Prevalence Study. Pediatrics 1992; 89: 525-584.
O.16 Growth hormone (GH) stimulates albumin but not muscle synthesis in HIV+ individuals M. A. McNurlan ~, P. J. Garlick ~, K. DeCristofaro 2, R. A. Frost 2, C. H.
Lang 1, R. Steigbigel 2, J. Fuhrer 2 and M. C. Gelato 2 Departments of ISurgery and 2Medicine, State University of New York, Stony Brook, NY, USA. HIV infection is associated with profound metabolic abnormalities, includ-
ing loss of lean body mass. The purpose of this study was to assess the effect of growth hormone (GH) administration on the synthesis of muscle protein and albumin in HIV + individuals. GH (Serono, Norwell, MA) was given at 6mg/d for 2 weeks, with dietary advice on increasing protein intake to 20% of energy. Serum GH levels were determined prior to treatment on samples taken every 20 rain between 22:00 and 06:00. Protein synthesis was measured, in fasting subjects prior to and after GH treatment, from the incorporation of L-[2H5]phenylalanine (45 mg/kg, 10-20 atoms %) into protein of the vastus lateralis muscle (5 control, 6 HIV) and plasma albumin (5 control, 8 HIV). Plasma GH levels in the HIV group were significantly lower than controls in both peak amplitude (22.1 -+7.0 (SEM) #g L-~ vs 4.2 _+0.7, P= 0.08) and the area under the concentration-time curve (77 +_40 #g L-~ 24 h-1 vs 6.4 _+ 2.2, P = 0.04). GH increased body weight in control (2.7 _+0.5 kg) and HIV (2.1 + 0.4 kg), and increased IGF-I 3- to 4-fold. Muscle protein synthesis increased by 40 _+ 19% in controls, but decreased by 29 _+ 18% in HIV+ subjects (control vs HIV, P = 0.03). In control subjects, albumin synthesis rose from 6.5 + 0.5% d-~ to 10.1 + 2.0 (P = 0.06), as a fraction of the intravascular albumin mass (FSR), and increased from 7.5 + 0.7gd -~ to tl .0 + 1.9 (P = 0.05), as the amount of albumin synthesized each day (ASR). In HIV+ subjects albumin FSR increased from 7.8 _+0.6% d-~ to 9.3 _+0.6 (P = 0.02), and ASR increased from 10.4 _+1.0 g d-~ to 12.5 _+1.1 (P = 0.03). GH treatment for 2 weeks resulted in the stimulation of albumin synLhesis in both control and HIV subjects. Muscle synthesis was stimulated in control subjects, but not in those with HIV infection. Thus, the pathological state alters the anabolic action of GH in a tissue specific manner.
3rd S e s s i o n - P E D I A T R I C S , E N T E R A L N U T R I T I O N
O.17 Acute effect of oral glutamine on whole body leucine and glutamine metabolism in Duchenne muscular dystrophy
O.18 The risk of dyslipoproteinaemia in obese children is influenced by apolipoprotein E polymorphism
R. Hankard, D. Hammond, M. Haymond and D. Darrnaun
Girardet** **Pediatric Gastroenterology and Nutrition, Trousseau Teaching Hospital, 26 Av. du Dr. A. Netter, 75571 Paris Cedex 12, France; *Biochemistry B, Saint-Antoine Teaching Hospital, 184 rue du Faubourg St.-Antoine, 75012 Paris, France.
Nemours Children's Clinic, Jacksonville, USA. Glutamine is thought to play a key role in protein homeostasis, and muscle mass loss in Duchenne muscular dystrophy (DMD) is associated with low intramuscular glutamine concentration. Previous studies have documented a protein sparing effect of glutarnine administration in stressed patients who have low intramuscular glutamine concentration, as well as in healthy humans. To determine whether glutamine has a protein anabolic effect in DMD, six 8- to 13-year-old DMD boys received 5-h intravenous infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state, and on 2 consecutive days while drinking: a) small, frequent sips of flavoured water on one day, and b) the same drink mixed with L-glutamine (800 ~mol.Kg -1.h -1), the other day. Body leucine (Ra.~eu) and glutamine (R ag=n) rate of appearance in plasma were determined from 13C-o~-ketoisocaproate, the intracelluiar metabolite of leucine, and ~SN-glutamine enrichments in plasma. Leucine oxidation rate (OX~eu)was calculated from 13CO2 enrichment in expired air, and the non-oxidative leucine disposal (NOLD), an index of protein synthesis, was: Ra.teu OXle u, Endogenous aa,gln (EndORa,gln) was calculated assuming that 50% of enteral glutamine reaches the bloodstream. Estimates of glutamine release from protein breakdown (Bgln), and glutamine de novo synthesis (Dgln) were calculated from Ra,~eu. Results are means _+SEM, statistical tests with paired t-test. During oral glutamine administration, aa,gln doubled from 321 _ 22 to 623 _+24#moI.Kg-~.h -~, P < 0.01, but EndoRa,g~n decreased from 321 _+22 to 247 +_241~moI.Kg-~.h -~, P = 0.01, resulting from a decrease in both Bgln (91 +- 4 vs 84 -+ 5 #moI.Kg -~.h -1, P < 0.01), and Dgln (230 +_21 vs 163 + 25 #mol.Kg-~.h -1, P = 0.02). During oral glutamine administration, R~,~eodecreased by 8% from 116 -+ 5 to 107 _+ 6#mol.Kg-~.h -~ ( P < 0.01), Ox~eudecreased by 35% from 23 _+2 to 15 _+ 2#mol.Kg-~.h -1 (P < 0.01), but NOLD did not change (93 -+ 4 vs 92 _+ 5 #mol.Kg -1 .h-1 , NS). Conclusions: These data suggest that in DMD children, acute oral glutamine administration: 1) is associated with a decrease in leucine release from protein degradation and might have a protein sparing effect inhibiting whole body protein breakdown, 2) inhibits endogenous glutamine production, therefore sparing nitrogen precursors. Further studies are warranted to determine the effect of long-term glutamine administration on muscle mass and function in DMD.
G. Parlier**, G. Thomas, G. BCrezait*, J. L. Fontaine** and J. Ph.
In adults, apoliprotein (Apo) E polymorphism modulates the consequences of obesity on lipid metabolism and patients with the ~2 and ~4 alleles are at increased risk of obesity-induced dyslipidemia. The purpose of this study was to determine whether Apo E polymorphism also influences the risk of dyslipidemia in obese children. Study population: We studied 137 non-genetically-related paediatfic patients (78 girls), aged 2.2-14.4 years (mean 9.9 -+ 3.1 years), with a body mass index greater than the 97th gender- and age-specific centile and a mean excess weight-for-height of 43.7 _+17.9%. Methods: (1) The Apo E genotype was determined by studying specific restriction profiles of ADN amplified by a PCR technique involving use of a pair of probes that recognized a specific sequence of exon 4 of the Apo E gene. (2) Total cholesterol (TC), HDL-cholesterol and triglycerides (TG) were assayed in fasting plasma samples taken before initiation of dietary treatment; LDL-cholesterol (LDL-C) was calculated using Friedwald's formula. Values for TC, TG, and LDL-C were classified as abnormal if they exceeded the 95th centile of values in the general paediatric population [1]. Results: The distribution of Apo E alleles was similar to that reported in the general Caucasian population (£2 = 6.2%; £3 = 82.1%, and s4 = 11.7%). (2) Fifty-five subjects (40.7%) had hyperlipidemia: 34 subjects (25.1%) with high LDL-C levels, including 23 with no other lipid abnormality and 32 subjects (23.4%) with high TG levels, including 21 with no other lipid abnormality. (3) The ~2 allele was associated with a higher prevalence of hypertriglyceridaemia as compared with the ~3 and E4 alleles (52.9% vs 19.5%, P < 0.05) Subjects with ~4 allele were more likely to have high LDL-C levels than subjects with the ~3 and ~2 alleles (34.7% vs 13.4%, P< 0.05). Conclusions: (1) Obesity is associated with a marked increase iin the risk of dyslipidemia even in childhood. (2) This risk is influenced by Apo E polymorphism, in particular by alleles ~2 and ~4, which have different effects on lipid metabolism.
Reference: [1] The LRC Prevalence Study. Pediatrics 1992; 89: 525-584.