Biomedical subjects

R Gougeon

Publications and source records attributed to R Gougeon.

At least 19 recordsLinked to original sources

PubMed2005

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover.

AIMS/HYPOTHESIS: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. MATWERIALS AND METHODS: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured. RESULTS: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75x in obese men and by 1.27x in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). CONCLUSIONS/INTERPRETATION: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

Adult↗

PubMed2002

The prediction of resting energy expenditure in type 2 diabetes mellitus is improved by factoring for glycemia.

BACKGROUND: Predictive equations have been reported to overestimate resting energy expenditure (REE) for obese persons. The presence of hyperglycemia results in elevated REE in obese persons with type 2 diabetes, and its effect on the validity of these equations is unknown. OBJECTIVE: We tested whether (1) indicators of diabetes control were independent associates of REE in type 2 diabetes and (2) their inclusion would improve predictive equations. DESIGN: A cross-sectional study of 65 (25 men, 40 women) obese type 2 diabetic subjects. Variables measured were: REE by ventilated-hood indirect calorimetry, body composition by bioimpedance analysis, body circumferences, fasting plasma glucose (FPG) and hemoglobin A(1c). Data were analyzed using stepwise multiple linear regression. RESULTS: REE, corrected for weight, fat-free mass, age and gender, was significantly greater with FPG>10 mmol/l (P=0.017) and correlated with FPG (P=0.013) and hemoglobin A(1c) as percentage upper limit of normal (P=0.02). Weight was the main determinant of REE. Together with hip circumference and FPG, it explained 81% of the variation. FPG improved the predictability of the equation by >3%. With poor glycemic control, it can represent an increase in REE of up to 8%. CONCLUSION: Our data indicate that in a population of obese subjects with type 2 diabetes mellitus, REE is better predicted when fasting plasma glucose is included as a variable.

Adult↗

PubMed2001

Effect of insulin and energy restriction on the thermic effect of protein in type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to test whether the thermic effect of oral protein is blunted in poorly controlled type 2 diabetes and is corrected by normalization of glycemia with insulin and 28 days of a very-low-energy diet. RESEARCH METHODS AND PROCEDURES: Resting energy expenditure (REE) and the thermic effect of 90 g of oral protein were measured, using indirect calorimetry, in nine (five women and four men) obese diabetic people [weight, 108 +/- 10 kg; waist circumference, 123 +/- 8 cm; body mass index, 40 +/- 3 kg/m(2)] who were hyperglycemic on day 8 or euglycemic with insulin on day 16 of a weight-maintaining diet and euglycemic on day 28 of a very low energy diet (VLED). Results were compared with those of seven (six women and one man) weight- and body mass index-matched obese nondiabetic subjects with a waist circumference of 111 +/- 6 cm. Substrates and hormonal responses were determined concurrently. RESULTS: Fasting glucose was normalized in the diabetic subjects with insulin from day 9 of VLED onward. Weight decreased in both groups by 9.9 +/- 0.9 kg with VLED. REE was 8 +/- 2% lower with insulin treatment and decreased by another 14 +/- 3% with VLED in the diabetic and by 15 +/- 1% in the nondiabetic subjects by week 4. After the protein meal, the thermic response was significantly (p < 0.05) less with hyperglycemia than with insulin-induced euglycemia, as percentage above REE (15.3 +/- 1.4 compared with 21.2 +/- 1.5%), as percentage of the energy content of the meal (19.5 +/- 1.5 compared with 25.2 +/- 1.7%), as kilocalories per 405 minutes (86 +/- 5 compared with 110 +/- 7), and less than in nondiabetic obese controls (21.0 +/- 2.2% above REE, 24.4 +/- 1.7% of energy of meal). After the VLED, the thermic effect of protein was significantly higher in both groups only as percentage above REE. The initial glucagon response was greater with hyperglycemia compared with euglycemia and post-VLED but not compared with the nondiabetic subjects. Hyperglycemia was associated with 21 +/- 4% greater urinary urea nitrogen excretion and urinary glucose losses of 134 +/- 50 mmol/d. DISCUSSION: This study shows a blunted thermic effect of protein in obese hyperglycemic type 2 diabetic subjects compared with matched nondiabetic subjects that can be corrected with insulin- or energy restriction-induced euglycemia.

Adult↗

PubMed2000

Distribution of protein turnover changes with age in humans as assessed by whole-body magnetic resonance image analysis to quantify tissue volumes.

We tested the hypothesis that nonmuscle lean tissue mass and its rate of protein catabolism remain constant with aging despite changes in the proportional contribution of these tissues to whole-body protein metabolism. Whole-body protein kinetics, using the 60-h oral [(15) N]glycine method, and muscle and nonmuscle protein catabolism, based on protein kinetic data, urinary N(tau)-methylhistine excretion and lean tissue volumes defined by whole-body magnetic resonance imaging, from eight healthy elderly subjects (5 females and 3 males, mean age 71.5 y) were compared with those of seven young persons (3 females and 4 males, mean age 28 y). There were no significant age or gender effects on rates of protein kinetics per L total lean tissue. There was a lower (P < 0.004) rate of muscle protein catabolism in the elderly (1.8 +/- 0.2 vs. 2.6 +/- 0.1 g. L(-1). d(-1)) and a trend (P = 0.08) for lower muscle volume (19.7 +/- 1.5 vs. 25.0 +/- 2.4 L). This contrasted with intraabdominal lean tissue, where the rate of protein catabolism (13. 8 +/- 0.6 vs. 13.2 +/- 0.9 g. L(-1 ). d(-1)) and volume (7.5 +/- 0.3 vs 8.0 +/- 0.5 L) did not differ between age groups. Thus, the decrease in the contribution by muscle to whole-body protein metabolism with age is associated with an increase from 62 to 74% (P < 0.001) in the contribution by nonmuscle lean tissues. These findings have potential implications for the nutrition of both normal and sick elderly persons.

Aged↗

PubMed2000

Glucoregulatory responses to intense exercise performed in the postprandial state.

A seven- to eightfold increment in hepatic glucose production (endogenous R(a)) occurs in postabsorptive (PA) intense exercise (IE). A similar response is likely present in the postprandial (PP) state, when most such exercise is performed, because 1) little evidence for increased intestinal absorption of glucose during exercise exists, and 2) intravenous glucose does not prevent it. We investigated IE in 10 PA and 8 PP fit, lean, young males who had exercised for 15 min at >84% maximum O(2) uptake, starting 3 h after a 412-kcal mixed meal. The meal induced a small rise in glycemia with sustained insulin and glucagon increases. Preexercise glucose total R(a) and utilization (R(d)) were equal and approximately 130% of the PA level. Exercise hyperglycemia in PP was delayed and diminished and, in early recovery, was of shorter duration and lesser magnitude (P = 0.042). Peak catecholamine (12- to 16-fold increase) and R(a) (PP: 11.5 +/- 1.4, PA: 13.8 +/- 1.4 mg. kg(-1). min(-1)) responses did not differ, and their responses during exercise were significantly correlated. Exercise glucagon, insulin, and glucagon-to-insulin responses were small or not significant. R(d) reached the same peak (PP: 8.0 +/- 0.6, PA: 9.3 +/- 0.8 mg. kg(-1). min(-1)) but was greater at 20-120 min of recovery in PP (P = 0.001). Therefore, the total R(a) response to IE is preserved despite the possibility of prior PP suppression of endogenous R(a) and is consistent with catecholamine mediation. Post-IE hyperglycemia is reduced in the postprandial state.

Adolescent↗

PubMed2000

Effects of oral hypoglycemic agents and diet on protein metabolism in type 2 diabetes.

OBJECTIVE: We tested whether oral hypoglycemic agents (OHA), gliclazide with or without metformin, during an isoenergetic (ISO) and then a low-energy diet (LED) improve the altered kinetics of whole-body protein metabolism in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 13 type 2 diabetic patients (aged 51+/-2 years, weight 110+/-5 kg, BMI 41+/-1 kg/m2, fasting glucose [FSG] 11.5+/-0.9 mmol/l) (means+/-SEM) and 10 obese control subjects (48+/-3 years, 98+/-6 kg, 37+/-2 kg/m2, FSG 5.5+/-0.3 mmol/l) consumed an ISO, 1.5 g x kg(-1) x day(-1) protein for a body weight corresponding to a BMI of 25 (BMI25), a formula diet (7 days for obese control subjects, 15 days for diabetic patients), and then a 28-day LED with 50% of the energy of ISO but the same protein intake (101+/-2 g/day). OHAs were given during ISO (days 8-15) and LED. On days 6-8 (and 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral 15N-glycine method was used to obtain nitrogen flux (Q), synthesis (S), and breakdown (B). Muscle protein catabolism was estimated from N(tau)-methylhistidine (3MH) excretion. RESULTS: During ISO with hyperglycemia, Q, and B adjusted for fat-free mass, sex, and age were higher and nitrogen balance and net endogenous protein synthesis (S-B) lower than in control subjects (P<0.05). OHA decreased FSG (9+/-1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, nitrogen retention, and S-B to levels in control subjects. The change in S-B correlated with that in FSG (r = -0.845, P = 0.001) and in fasting plasma C-peptide (r = 0.852, P = 0.0005). With LED and OHA, weight decreased 6.3 kg, glycemia reached near-normal levels, and nitrogen equilibrium was maintained; Q decreased by 7%, S and B by 11% (P<0.05) to values found in control subjects. CONCLUSIONS: OHA during ISO corrected protein turnover in relation to glycemia and plasma C-peptide. The LED maintained protein homeostasis in obese control subjects and, in diabetes patients with OHA, normalized protein metabolism. These findings have implications for diet and OHA prescription.

Blood Glucose↗

PubMed1999

19F/29Si distance determination in fluoride-containing octadecasil by Hartmann-Hahn cross-polarization under fast magic-angle spinning.

19F/29Si Hartmann-Hahn continuous wave cross-polarization (CP) has been applied under fast magic-angle spinning (MAS) to a powder sample of octadecasil. Strong oscillations occur during CP on a sideband matching condition between the isolated 29Si-19F spin pairs formed by the silicons in the D4R units and the fluoride anions. The magnitude of the dipolar coupling constant was deduced directly from the line-splitting between the intense singularities of the Pake-like patterns obtained by Fourier transformation of the oscillatory polarization transfer. The corresponding Si-F internuclear distance, r = 2.62 +/- 0.05 A, is found to be in very good agreement with the X-ray crystal structure and the value of 2.69 +/- 0.04 A recently reported from rotational echo double resonance (REDOR) and transferred echo double resonance (TEDOR) nuclear magnetic resonance (NMR) experiments. Furthermore, the CP technique is still reliable under fast MAS where both REDOR and TEDOR sequences suffer from severe artefacts due to finite pulse lengths. In octadecasil, a spinning frequency of approximately 14 kHz is shown to be necessary for an effective suppression of 19F-19F spin diffusion. The influences of experimental missettings and radiofrequency (RF) field inhomogeneity are taken into account.

Fluorides↗

PubMed1999

Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women.

BACKGROUND: Plasma leptin in humans is subject to both long- and short-term regulation; it correlates with indexes of body fat that can only change slowly. However, short-term fasting causes large and rapid decreases. OBJECTIVE: We tested the interactions between energy intake and fat loss on plasma leptin during prolonged moderate and severe energy restriction, with a view to understanding mechanisms of control. DESIGN: Postabsorptive leptin was measured with an enzyme-linked immunosorbent assay specific for the human peptide in 21 obese women aged 41 +/- 3 y (weight: 102 +/- 4 kg; 48 +/- 1% body fat) after 1 wk of a weight-maintaining diet and then weekly for 4 wk during a total fast (group 1); a 1.9-MJ/d all-protein, very-low-energy diet (VLED) (group 2); or a low-energy, balanced-deficit diet (BDD) providing 50% of maintenance energy (group 3). In groups 1 and 2, leptin was also measured after 1 wk of refeeding with a diet equivalent to the BDD. RESULTS: Mean leptin decreased markedly by up to 66% (P < 0.001) at week 1 of energy restriction and then gradually thereafter. The change in leptin per kilogram fat mass correlated with that in glucose concentrations [r = 0.538 (P = 0.012) at week 1 and r = 0.447 (P = 0.042) at week 4] but not with that in fat mass. During refeeding postfasting, leptin increased (P = 0.008), despite an ongoing loss of fat mass and correlated positively with changes in resting energy expenditure. At times with comparable cumulative energy restriction and fat loss between diets, the percentage change in leptin paralleled that in glucose. CONCLUSIONS: In obesity, changes in energy intake over days to weeks are a primary modulator of plasma leptin concentrations that are related to the change in glycemia and are able to override the regulatory influence of fat mass.

Adult↗

PubMed1998

Effect of exogenous insulin on protein metabolism with differing nonprotein energy intakes in Type 2 diabetes mellitus.

OBJECTIVE: To determine if insulin treatment combined with a generous protein intake would normalize whole-body protein kinetics and nitrogen balance in obese subjects with Type 2 diabetes mellitus when compared to obese nondiabetic subjects: 1) during weight-maintenance and 2) after a very low energy diet (VLED). DESIGN: Clinical intervention study of iso- followed by hypoenergetic feedings with or without exogenous insulin. SUBJECTS: Sixteen obese subjects with a body mass index (BMI) of 39+/-4 kg/m2, with Type 2 diabetes mellitus (three men, six women) or without (one man, six women). MEASUREMENTS: Nitrogen flux rate calculated from the urine 15N-urea enrichment by using the 60 h oral 15N-glycine method, rates of protein synthesis and breakdown calculated from nitrogen flux on days 6-8 (and 13-15 in the diabetic subjects) of isoenergetic feeding and days 24-26 of a 1.9 MJ diet. RESULTS: With insulin therapy: 1) during isoenergetic feeding, in the hyperglycaemic diabetic subjects, nitrogen balance was significantly less than in the obese controls (-0.6+/-0.6 compared with +1.8+/-0.9 g N/d, P = 0.037) but became positive (+2.6+/-0.6 g N/d, P < 0.05); nitrogen flux decreased and net protein synthesis increased from values different from those of the obese controls to values no longer different; 2) during the VLED, plasma glucose concentrations < 7 mmol/L were achieved and maintained in all diabetic subjects. Nitrogen equilibrium observed in five out of seven obese nondiabetic and four out of nine diabetic subjects was associated with no change in nitrogen flux from the euglycaemic isoenergetic studies, but with 17% and 23% lower rates of synthesis (P < 0.05) and 7% and 15% lower rates of breakdown (NS) in nondiabetic and diabetic subjects, respectively. CONCLUSION: Sufficient exogenous insulin to near-normalize glycaemia improves the altered protein metabolism in hyperglycaemic diabetic subjects during isoenergetic feeding, and restores nitrogen equilibrium better than with VLED alone. Protein metabolism is more sensitive to the state of diabetes control than is generally appreciated 'clinically'.

Adult↗

PubMed1997

Effect of glycemic control on the kinetics of whole-body protein metabolism in obese subjects with non-insulin-dependent diabetes mellitus during iso- and hypoenergetic feeding.

We postulated whether interventions capable of restoring euglycemia would correct whole-body protein metabolism, shown previously to be elevated in hyperglycemic persons with non-insulin-dependent diabetes (NIDDM). The kinetics of protein metabolism were estimated in obese subjects with NIDDM in the hyper- and normoglycemic states during isoenergetic feeding and in the normoglycemic state induced by 4 wk of a very-low-energy diet (VLED) with constant protein intake. Seven NIDDM subjects [three males and four females with a body mass index (in kg/m2) of 39 +/- 2] were given a weight-maintaining, liquid formula providing 95 g protein/d for 15 d, followed in six subjects (two males and four females) for 27 d by a diet providing 1.7 MJ, 93 g protein derived from casein-soy, 13 g carbohydrate, 2 g fat, multivitamins and minerals, and a potassium bicarbonate supplement (32 mmol) per day. Exogenous insulin was given to achieve normoglycemia during the first 8 d of isoenergetic feeding. On days 6-8, 12-14, and 25-27, nitrogen flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain "integrated" feeding and fasting values. Rates of synthesis and breakdown were calculated from nitrogen flux. During isoenergetic feeding, normoglycemia was associated with more positive nitrogen balance (2.6 +/- 0.5 compared with -0.6 +/- 0.6 g N/d, P < 0.05); 18-23% lower nitrogen flux, and synthesis and breakdown rates (P < 0.05), and a 3% decrease in resting energy expenditure (P < 0.05). During the VLED, euglycemia was achieved but nitrogen balance, although it became less negative with time, never reached equilibrium. This was associated with significant (P < 0.05) decreases in the synthesis rate, resulting in net protein losses. Thus, the altered protein metabolism in moderately hyperglycemic NIDDM subjects was improved with exogenous insulin in doses sufficient to restore normoglycemia in the isoenergetic fed state, but it remained abnormal with a reduced non-protein energy intake. This suggests that protein metabolism is more sensitive to insulinization than was thought previously.

Adult↗

PubMed1997

Whole-body protein turnover in the healthy elderly.

We tested the hypothesis that aging affects whole-body protein turnover via altered fat-free mass (FFM). Whole-body protein kinetics were estimated by the 60-h oral [15N]glycine method. Results from 16 healthy, elderly subjects (8 men and 8 women with a mean age of 72.6 y) were compared for age and sex effects with those of 15 lean young subjects (8 men and 7 women with a mean age of 28.4 y) during isoenergetic formula diets. Per kilogram body weight, nitrogen flux was lower only as an effect of age (P = 0.006) whereas age and female sex significantly lowered synthesis and breakdown (P < or = 0.04). However, per kilogram FFM, no significant age or sex effects on rates of protein kinetics remained. Age and female sex contributed significantly to decreased muscle protein catabolism (based on 3-methylhistidine excretion), both in absolute terms and as a percentage of whole-body protein breakdown in the elderly compared with the young: 20.2% compared with 30.9% in women and 27.9% compared with 39.8% in men. No significant age or sex effects on rates of nonmuscle lean tissue protein breakdown were observed with or without correction for body composition. We conclude that the lower rates of flux, synthesis, and breakdown per kilogram body weight in elderly compared with young persons are due to changes in body composition with aging because rates are not different per kilogram FFM. However, there is a reduced contribution by muscle to whole-body protein catabolism in older persons. This has potential implications for the nutrition of both normal and sick elderly persons.

Adult↗

PubMed1996

Thermic and metabolic responses to oral glucose in obese subjects with non-insulin-dependent diabetes mellitus treated with insulin or a very-low-energy diet.

Increased resting energy expenditure (REE) and a blunted thermic effect of glucose (TEF) have been reported in obese subjects with non-insulin-dependent diabetes mellitus (NIDDM). I questioned whether the abnormal REE and TEF would be corrected by normalizing glycemia with insulin or a very-low-energy diet (VLED). Three male and four female obese subjects with NIDDM [weighing 108 +/- 6 kg and with body mass index (in kg/m2) of 39 +/- 2] received a weight-maintaing formula diet containing 95 g protein/d for 15 d then a 1.7-MJ, 93-g-protein VLED for 27 d. Insulin was given from days 1 to 8 in doses sufficient to normalize glycemia. REE was measured weekly and TEF was measured on days 8 and 15 of isoenergetic feeding and 28 d after the VLED by using a ventilated-hood indirect calorimeter. Weight decreased 9.8 +/- 1 kg during the VLED. REE was 3% lower with insulin treatment than during hyperglycemia (7878 +/- 364 compared with 8125 +/- 381 kJ/d, P = 0.002). REE decreased by 20% to 6494 +/- 280 kJ/d by week 4 of the VLED. After 112 g oral glucose, increments in energy expenditure were significantly greater during isoenergetic feeding with insulin than without (7.5 +/- 1.3% compared with 4.3 +/- 0.9% above REE) and after the VLED (10.5 +/- 1.0% above REE, P < 0.05). Plasma glucose excursions were greatest without exogenous insulin (peak 21.5 +/- 1.8 mmol/L at 120 min, 16.3 +/- 1.9 mmol/L at 225 min). Plasma fatty acid excursions were the lowest with insulin treatment. The integrated plasma glucose and fatty acid responses above baseline did not differ among studies; the integrated insulin and C-peptide responses were greater after the VLED. Cumulative nonoxidative glucose disposal (stored glucose) was higher with insulin therapy than without (52 +/- 6 compared with 35 +/- 7 g/210 min, P < 0.05) and increased significantly to 66 +/- 6 g after the VLED (compared with the isoenergetic diet without insulin). TEF correlated significantly with integrated C-peptide and insulin responses. The percentage increase in TEF with euglycemia (with insulin and VLED) correlated with the percentage increase in stored glucose (P < 0.05). The greater TEF was associated with a greater insulin response, which was probably responsible for the greater stored glucose.

Adult↗

PubMed1995

1H solid-state nuclear magnetic resonance study of the mobility of the tetrapropylammonium template in a purely siliceous MFI-type zeolite.

Dynamics of tetrapropylammonium (TPA) cation occluded during the synthesis in a siliceous MFI zeolite is investigated by 1H broad-line nuclear magnetic resonance (NMR) methods. Second moments M2, spin-lattice relaxation times T1 and T1 rho are measured in a large temperature domain. To al comparison, similar measurements are also reported in bulk tetrapropylammonium bromide (TPABr). Whereas methyl reorientation at low temperature and tumbling of the cation in the plastic phase are observed in crystalline TPABr in accordance with published studies, a new slower motion which could not be identified is observed below the phase transition. Such a motion is much more clearly shown by the existence of a minimum of T1 rho in a quenched sample. Our measurements in the zeolite demonstrate that the TPA template exhibits a larger and more complex mobility below 378 K. Beyond the fast methyl reorientation, the results disclose a motion which probably involves the entire propyl arms inside the channels. So the zeolite framework seems to make such a kind of motion easier. On the contrary, even at 450 K, the highest temperature investigated, the tumbling which would necessitate exchange of the propyl arms between the channels is not observed. A slow motion, responsible for a decrease of T1 rho above 350 K, could not be identified. While a simple correlation time is sufficient to describe the relaxation time dependences in TPABr, a distribution (such as Williams-Watts) is required to account for those in the zeolite.

Magnetic Resonance Spectroscopy↗

PubMed1995

Response of plasma ASP to a prolonged fast.

OBJECTIVE: To determine the changes in the plasma level of acylation stimulating protein (ASP) during a one month total fast in female subjects with marked obesity. DESIGN: Patients with marked obesity underwent a month total fast, before, during (2 weeks), and at the end of which, a variety of relevant metabolic parameters were measured. SETTING: A metabolic unit of a teaching hospital. SUBJECTS: 10 women with marked obesity were studied and the results compared with those in 16 age-matched controls. MAIN OUTCOME MEASURES: Plasma ASP, lipoprotein lipids, apoB, free fatty acid, and ketone levels. RESULTS: At baseline, fasting levels of ASP in the obese group were double that in control subjects (116 +/- 26 vs 53 +/- 30 nM P < 0.001). During the fast, ASP levels dropped progressively and were within the normal range at the end of the study (63 +/- 16 vs 53 +/- 30 nM pNS). In addition, there was a strong correlation between the plasma ASP at baseline before beginning the fast and the 4 week drop in ASP. That is, those subjects who had the highest starting ASP also had the largest 4 week drop in ASP (r2 = 0.644, P < 0.005). Of interest, as plasma ASP levels dropped, plasma free fatty acid and ketone levels rose and when all timepoints were considered, there was a significant inverse relation between plasma ASP and plasma free fatty acid (r2 = 0.295, P < 0.0002). CONCLUSIONS: The pattern of responses during the fast is that of increasing mobilization of fatty acids from adipose tissue coincident with decreased activity of the pathway responsible for the storage of adipocyte triglyceride mass. The data are consistent, therefore, with the role proposed for ASP as a major determinant of the rate of triglyceride synthesis in human adipocytes and thus a potentially important factor in the pathophysiology of obesity.

Adult↗

PubMed1995

Whole-body protein turnover in obese subjects during two very low energy diets of differing amino acid composition.

OBJECTIVE: To determine whether the kinetics of protein metabolism would differ with the prolonged use of a casein-soy 96 g protein, 1.7MJ/d very low energy diet (VLED) from those of a tryptophan- and methionine-supplemented hydrolyzed collagen VLED, in obesity. DESIGN: Clinical intervention study of 1 week isoenergetic diet followed by 6 weeks VLED. SUBJECTS: 6 (1M,5F) healthy obese subjects (age: 38 +/- 4 y, BMI: 33 +/- 1 kg/m2, weight: 97 +/- 7 kg). MEASUREMENTS: Whole-body nitrogen (N) flux rate (Q) from 15N abundance in urinary urea using the oral 15N-glycine method and rates of protein synthesis (S) and breakdown (B) calculated from Q; N balance; resting metabolic rate; metabolic and hormonal responses. RESULTS: Q (per kg LBM) was maintained with both collagen and casein-soy VLED. S and B decreased (P < 0.05) at week 4 of both VLEDs with resulting decreases in net protein synthesis. At week 6, S decreased with both VLEDs, but B decreased only with casein-soy, at which time N balance was at equilibrium with casein-soy but returned to negative with collagen. Initial resting metabolic rate correlated with baseline Q and S. It decreased by 16% with the VLEDs; 25% of the decrease may derive from the decline in S. CONCLUSION: A 6 week casein-soy VLED with 46% of amino acids as essential does not provide a substantial advantage compared to hydrolyzed collagen with 16% of amino acids as essential. With prolonged use, it may better maintain N equilibrium by preventing further increments in protein breakdown.

Adult↗

PubMed1994

Effect of NIDDM on the kinetics of whole-body protein metabolism.

We postulated that dietary protein utilization and body protein metabolism are altered in hyperglycemic individuals with non-insulin-dependent diabetes mellitus (NIDDM). This was tested by estimating the kinetics of protein metabolism in obese NIDDM patients in the hyperglycemic state of isoenergetic feeding and in the normoglycemic state induced by the prolonged use of a very-low-energy diet (VLED) and comparing them with results in obese nondiabetic subjects studied previously. Seven obese subjects with NIDDM (one male, six females, body mass index = 35.8 +/- 2.0 kg/m2) were given a 1.7 MJ (410 kcal) all protein (93 g/day) diet derived from hydrolyzed collagen and supplemented with tryptophan and methionine, which provides 16% of its amino acids as essential, a multivitamin and mineral supplement, and 16 mmol KCl for 42 days. During the seven-day isoenergetic diet and at weeks 4 and 6 of the VLED, amino nitrogen (N) flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain the integrated feeding-fasting metabolism. Rates of synthesis (S) and breakdown (B) were calculated from N flux. At day 7 of the isoenergetic diet, whole-body N flux, S, B, and resting metabolic rate (RMR) were 12-24% greater (P < 0.05) in the NIDDM subjects than observed in nondiabetic obese subjects. Mean plasma glucose decreased (P < 0.05) from the isoenergetic period (14.9 +/- 2.4 mM) to 7.2 +/- 1.2 mM at week 4 and 6.5 +/- 1.1 mM at week 6 of the VLED. RMR declined progressively by 25% at week 5 of the VLED. Corresponding significant (P < 0.05) decreases from isoenergetic feeding to weeks 4 and 6 of the VLED occurred in whole-body N flux (from 51 +/- 2 to 42 +/- 1 g N/day), in S (from 38 +/- 3 to 24 +/- 1 g N/day), and in B (from 39 +/- 3 to 26 +/- 1 g N/day) resulting in net losses (S-B). S-B was significantly more negative (P < 0.05) in NIDDM than in the nondiabetic obese subjects at week 4 (-1.5 +/- 0.5 vs. 0.9 +/- 0.3 g N/day) but not at week 6 (-1.3 +/- 0.4 vs. -0.9 +/- 4 g N/day). During the VLED, N balance became less negative with time but never reached equilibrium in NIDDM. Thus, abnormal protein metabolism is present in NIDDM in the isoenergetic fed state with moderate hyperglycemia and persists during a VLED that restores glycemia to near normal.

Adult↗

PubMed1992

Protein metabolism in obese subjects during a very-low-energy diet.

We postulated that the return to nitrogen equilibrium after 3 wk of a negative balance during a very-low-calorie diet (VLCD) providing low-quality protein in obese subjects was due to availability of endogenously originating amino acids from a "pool" that, when depleted, would result in worsening balance. This should be reflected in altered kinetics of protein metabolism with the requirement for increased breakdown to maintain synthesis constant. Seven female obese subjects [body mass index (BMI) = 34.4 +/- 1.8 kg/m2] were given a 1.7-MJ/d all-protein diet (16.8 g N) derived from hydrolyzed gelatin (supplemented with tryptophan and methionine) that provides 18% of its amino acids as essential, a multivitamin-mineral supplement, and 16 mmol KCl for 42 d. At baseline (7-d isocaloric diet), and weeks 4 and 6 of VLCD, amino nitrogen flux rate was calculated from the 15N abundance in urinary urea using the oral 15N-glycine method and rates of synthesis (S) and breakdown (B) inferred from N flux. Whole-body N flux did not change from baseline to weeks 4 and 6 (39.5 +/- 2.0 vs 37.4 +/- 2.0 vs 39.2 +/- 1.9 g N/d). By contrast, S and B decreased at weeks 4 and 6 with S decreasing more so that net protein synthesis (S-B) was less positive at week 4 than at baseline (2.2 +/- 0.2 and 0.9 +/- 0.3 g N/d; P less than 0.05) and became negative at week 6 (-0.9 +/- 0.2 g N/d; P less than 0.05). Concurrently, N equilibrium was achieved by week 4 but returned to negative balance by week 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1992

The metabolic response to two very low energy diets (VLED) of differing amino acid composition during weight reduction.

Nitrogen (N) sparing and even equilibrium have been achieved in obese subjects with all-protein weight-reducing very low energy diets (VLED) apparently independently of the content of essential amino acids. This study assessed whether the metabolic response observed at week 3 of an all-protein VLED with 46% of amino acids (aa) as essential was modified during week 4, when consuming a protein source that provided 16% of amino acids as essential. Six healthy obese subjects (BMI: 35.3 +/- 1.3 kg/m2, weight 90 +/- 9 kg) were given a 1.72 MJ (400 kcal) all protein (93 g) VLED and a multi-vitamin-mineral supplement daily for four weeks. During weeks 1 to 3, the protein was casein-soy (46% essential aa) and during week 4, tryptophan- and methionine-supplemented collagen hydrolysate (16% essential aa). At week 3, decreases in plasma glucose, insulin, cholesterol, blood pH and bicarbonate, and increases in plasma free fatty acids, serum urea, uric acid and blood and urine ketones occurred compared to baseline. These adaptations were unchanged at week 4. N balance returned toward equilibrium by day 23 remaining at values close to 0 despite the change in diet composition. Mean negative N balance did not differ between weeks 3 and 4 (-1.1 +/- 0.5 g vs. -0.6 +/- 0.5 g/day) and neither did mean urinary ammonium N excretion (0.71 +/- 0.08 vs. 0.73 +/- 0.07 g/day). Urinary urea N excretion tended to increase with the collagen-based diet reflecting the greater proportion of N in this protein source (18 vs. 15%).(ABSTRACT TRUNCATED AT 250 WORDS)

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