scholarly journals Carbohydrate, Protein, and Fat Metabolism during Exercise after Oral Carnitine Supplementation in Humans

2008 ◽  
Vol 18 (6) ◽  
pp. 567-584 ◽  
Author(s):  
Elizabeth M. Broad ◽  
Ronald J. Maughan ◽  
Stuart D.R Galloway
Keyword(s):  
Metabolic Stress ◽  
Nitrogen Excretion ◽  
Moderate Intensity ◽  
Acid Oxidation ◽  
Plasma Urea ◽  
Branched Chain Amino Acid ◽  
Before And After ◽  
Branched Chain ◽  
Response To Exercise ◽  
To Receive

Twenty nonvegetarian active males were pair-matched and randomly assigned to receive 2 g of L-carnitine L-tartrate (LC) or placebo per day for 2 wk. Participants exercised for 90 min at 70% VO2max after 2 days of a prescribed diet (M ±SD: 13.6 ± 1.6 MJ, 57% carbohydrate, 15% protein, 26% fat, 2% alcohol) before and after supplementation. Results indicated no change in carbohydrate oxidation, nitrogen excretion, branched-chain amino acid oxidation, or plasma urea during exercise between the beginning and end of supplementation in either group. After 2 wk of LC supplementation the plasma ammonia response to exercise tended to be suppressed (0 vs. 2 wk at 60 min exercise, 97 ± 26 vs. 80 ± 9, and 90 min exercise, 116 ± 47 vs. 87 ± 25 μmol/L), with no change in the placebo group. The data indicate that 2 wk of LC supplementation does not affect fat, carbohydrate, and protein contribution to metabolism during prolonged moderate-intensity cycling exercise. The tendency toward suppressed ammonia accumulation, however, indicates that oral LC supplementation might have the potential to reduce the metabolic stress of exercise or alter ammonia production or removal, which warrants further investigation.

scholarly journals Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Shivraj Grewal ◽  
Sriram Gubbi ◽  
Andin Fosam ◽  
Caroline Sedmak ◽  
Shanaz Sikder ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Metabolomic Analysis ◽  
Metabolomic Profiling ◽  
Branched Chain Amino Acid ◽  
Before And After ◽  
Branched Chain

Abstract Context and Objective Leptin treatment has dramatic clinical effects on glucose and lipid metabolism in leptin-deficient patients with lipodystrophy. Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy. Study Design We conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measuring changes in physiologically relevant metabolites before and after leptin therapy. Results Metabolomic analysis revealed changes in pathways involving branched-chain amino acid metabolism, fatty acid oxidation, protein degradation, urea cycle, tryptophan metabolism, nucleotide catabolism, vitamin E, and steroid metabolism. Fold changes in pre- to post-treatment metabolite levels indicated increased breakdown of fatty acids, branched chain amino acids proteins, and nucleic acids. Conclusions Leptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy. Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.

scholarly journals Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy

2020 ◽  
Vol 150 (12) ◽  
pp. 3180-3189
Author(s):  
Hong Chang Tan ◽  
Jean W Hsu ◽  
Jean-Paul Kovalik ◽  
Alvin Eng ◽  
Weng Hoong Chan ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Sleeve Gastrectomy ◽  
Plasma Concentrations ◽  
Fat Free Mass ◽  
Acid Oxidation ◽  
Morbidly Obese ◽  
Healthy Weight ◽  
Leucine Oxidation ◽  
Branched Chain Amino Acid ◽  
Branched Chain

ABSTRACT Background Plasma concentrations of branched-chain amino acids (BCAAs) are elevated in obese individuals with insulin resistance (IR) and decrease after bariatric surgery. However, the metabolic mechanisms are unclear. Objectives Our objectives are to compare leucine kinetics between morbidly obese and healthy-weight individuals cross-sectionally, and to prospectively evaluate changes in the morbidly obese after sleeve gastrectomy. We hypothesized that leucine oxidation is slower in obese individuals and increases after surgery. Methods Ten morbidly obese [BMI (in kg/m2) ≥32.5, age 21–50 y] and 10 healthy-weight participants (BMI <25), matched for age (median ∼30 y) but not gender, were infused with [U-13C6] leucine and [2H5] glycerol to quantify leucine and glycerol kinetics. Morbidly obese participants were studied again 6 mo postsurgery. Primary outcomes were kinetic parameters related to BCAA metabolism. Data were analyzed by nonparametric methods and presented as median (IQR). Results Participants with obesity had IR with an HOMA-IR (4.89; 4.36–8.76) greater than that of healthy-weight participants (1.32; 0.99–1.49; P < 0.001) and had significantly faster leucine flux [218; 196–259 compared with 145; 138–149 μmol · kg fat-free mass (FFM)−1 · h−1], oxidation (24.0; 17.9–29.8 compared with 16.1; 14.3–18.5 μmol · kg FFM−1 · h−1), and nonoxidative disposal (204; 190–247 compared with 138; 129–140 μmol · kg FFM−1 · h−1) (P < 0.017 for all). After surgery, the morbidly obese had a marked improvement in IR (3.54; 3.06–6.08; P = 0.008) and significant reductions in BCAA concentrations (113; 95–157 μmol/L) and leucine oxidation (9.37; 6.85–15.2 μmol · kg FFM−1 · h−1) (P = 0.017 for both). Further, leucine flux in this group correlated significantly with IR (r = 0.78, P < 0.001). Conclusions BCAA oxidation is not impaired but elevated in individuals with morbid obesity. Plasma BCAA concentrations are lowered after surgery owing to slower breakdown of body proteins as insulin's ability to suppress proteolysis is restored. These findings suggest that IR is the underlying cause and not the consequence of elevated BCAAs in obesity.

scholarly journals 120 Effects of dietary leucine concentration on branched-chain amino acid metabolism in growing pigs

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 65-66
Author(s):  
Woong B Kwon ◽  
Kevin J Touchette ◽  
Aude Simongiovanni ◽  
Kostas Syriopoulos ◽  
Anna Wessels ◽  
...  
Keyword(s):  
Growth Performance ◽  
Average Daily Gain ◽  
Growing Pigs ◽  
Feed Ratio ◽  
Final Body Weight ◽  
Plasma Urea ◽  
Biological Value ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Quadratic Effects

Abstract The hypothesis that excess dietary Leu affects growth performance and metabolism of branched-chain amino acids (BCAA) in growing pigs was tested. Forty barrows (30.0 ± 2.7 kg) were placed in metabolism crates and randomly allotted to 5 diets that contained 100, 150, 200, 250, or 300% of the requirement for standardized ileal digestible Leu. Initial and final body weight of pigs and daily feed provisions were recorded. Urine and fecal samples were collected for 5 d to measure N balance and biological value of diets. At the conclusion of the experiment, blood, brain, liver, and muscle samples were collected and average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were calculated. Orthogonal polynomial contrasts were used to determine linear and quadratic effects of increasing Leu in the diets. Results indicated that ADG, ADFI, and G:F decreased (linear, P < 0.05) as dietary Leu increased (Table 1). A trend (linear, P = 0.082) for decreased N retention and decreased (linear, P < 0.05) biological value of protein was also observed. Plasma urea N increased (linear, P < 0.05) and a quadratic reduction (P < 0.05) in plasma serotonin and a linear reduction (P < 0.05) in cerebral serotonin were observed with increasing dietary Leu. Concentrations of BCAA in liver increased (linear, P < 0.001), concentrations of BCAA in muscle decreased (linear, P < 0.05), concentration of α-keto-isovalerate was reduced (linear and quadratic, P < 0.001) in liver, muscle, and serum, and α-keto-β-methylvalerate was reduced (linear and quadratic, P < 0.001) in muscle and serum, whereas α-keto-isocaproate increased (linear, P < 0.05) in liver and muscle, and in serum (linear and quadratic, P < 0.001) with increasing dietary Leu. In conclusion, excess dietary Leu reduced growth performance and cerebral serotonin and tended to reduce protein synthesis.

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

1978 ◽  
Vol 234 (5) ◽  
pp. E494 ◽  
Author(s):  
H S Paul ◽  
S A Adibi
Keyword(s):  
Amino Acids ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Acid Oxidation ◽  
Acyltransferase Activity ◽  
Remarkable Effect ◽  
Carnitine Acyltransferase ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

scholarly journals Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine

1985 ◽  
Vol 227 (2) ◽  
pp. 651-660 ◽  
Author(s):  
T W Stephens ◽  
A J Higgins ◽  
G A Cook ◽  
R A Harris
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Fatty Acid Oxidation ◽  
Carnitine Palmitoyltransferase ◽  
Partial Purification ◽  
Acid Oxidation ◽  
Branched Chain Amino Acid ◽  
Malonyl Coa ◽  
Carnitine Palmitoyltransferase I ◽  
Branched Chain

Oxfenicine [S-2-(4-hydroxyphenyl)glycine] is transaminated in heart and liver to 4-hydroxyphenylglyoxylate, an inhibitor of fatty acid oxidation shown in this study to act at the level of carnitine palmitoyltransferase I (EC 2.3.1.21). Oxfenicine was an effective inhibitor of fatty acid oxidation in heart, but not in liver. Tissue specificity of oxfenicine inhibition of fatty acid oxidation was due to greater oxfenicine transaminase activity in heart and to greater sensitivity of heart carnitine palmitoyltransferase I to inhibition by 4-hydroxyphenylglyoxylate [I50 (concentration giving 50% inhibition) of 11 and 510 microM for the enzymes of heart and liver mitochondria, respectively]. Branched-chain-amino-acid aminotransferase (isoenzyme I, EC 2.6.1.42) was responsible for the transamination of oxfenicine in heart. A positive correlation was found between the capacity of various tissues to transaminate oxfenicine and the known content of branched-chain-amino-acid aminotransferase in these tissues. Out of three observed liver oxfenicine aminotransferase activities, one may correspond to asparagine aminotransferase, but the major activity could not be identified by partial purification and characterization. As reported previously for malonyl-CoA inhibition of carnitine palmitoyltransferase I, 4-hydroxyphenylglyoxylate inhibition of this enzyme was found to be very pH-dependent. In striking contrast with the kinetics of malonyl-CoA inhibition, 4-hydroxyphenylglyoxylate inhibition was not affected by oleoyl-CoA concentration, but was partially reversed by increasing carnitine concentrations.

New tools for an old question: dependence of ATP and bicarbonate for branched-chain keto acids oxidation

2019 ◽  
Vol 476 (15) ◽  
pp. 2235-2237
Author(s):  
Henver S. Brunetta ◽  
Graham P. Holloway
Keyword(s):  
Energy Production ◽  
Acid Oxidation ◽  
Methodological Issues ◽  
Amino Acid Oxidation ◽  
Branched Chain Amino Acid ◽  
Biochemical Journal ◽  
Keto Acids ◽  
Branched Chain ◽  
Branched Chain Keto Acids

Abstract Branched-chain keto acids (BCKA) metabolism involves several well-regulated steps within mitochondria, requires cofactors, and is modulated according to the metabolic status of the cells. This regulation has made it challenging to utilize in vitro approaches to determine the contribution of branched-chain amino acid oxidation to energy production. These methodological issues were elegantly addressed in a recent publication within the Biochemical Journal. In this issue, Goldberg et al. [Biochem. J. (2019) 476, 1521–1537] demonstrated in a well-designed system the dependence of ATP and bicarbonate for BCKA full oxidation. In addition, the utilized system allowed the authors to characterize specific biochemical routes within mitochondria for each BCKA. Among them, a quantitative analysis of the participation of BCKA on mitochondrial flux was estimated between tissues. These findings are milestones with meaningful impact in several fields of metabolism.

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