scholarly journals Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 355 ◽  
Author(s):  
Jérémie David ◽  
Dominique Dardevet ◽  
Laurent Mosoni ◽  
Isabelle Savary-Auzeloux ◽  
Sergio Polakof

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

2004 ◽  
Vol 23 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Toyohisa Katsumata ◽  
Nobuo Nishimura ◽  
Kazunori Mawatari ◽  
...  

Branched-chain amino acids (l-isoleucine, l-valine, and l-leucine) are being increasingly used in sport supplements. This study evaluated toxicological and behavioral effects of l-isoleucine (Ile), l-valine (Val), and l-leucine (Leu) during a dosing study with male and female Sprague-Dawley rats. The amino acids were incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w). A control group of rats received a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine stability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. No significant, dose-related effects on body weight were found in rats fed a Leu-and Ile-supplemented diet. Val mixed into a diet at 5.0% ( w/ w) decreased slightly, but significantly body weight gain in females, but not males. Ile (5.0% w/ w) affected the urine electrolytes, protein, ketone bodies, urine glucose, and urobilinogen in both genders, yet the observed changes remained mostly within the range observed in controls. The random findings in hepatology and ophthalmology at the 13-week sacrifice were not considered toxicologically relevant to effects of the tested amino acids. No significant changes in organ weights were recorded. We estimate the no-observed-adverse-effect level (NOAEL) for Ile at 2.5% for both genders (male, 1.565 ± 0.060 g/kg/day; females, 1.646 ± 0.095 g/kg/day), Val at 5.0% for males (3.225 ± 0.135 g/kg/day) and 2.5% for females (1.853 ± 0.060 g/kg/day), and Leu at 5.0% for both genders (males, 3.333 ± 0.101 g/kg/day: females, 3.835 ± 0.257 g/kg/day).


2000 ◽  
Vol 84 (2) ◽  
pp. 157-163 ◽  
Author(s):  
T. Obitsu ◽  
D. Bremner ◽  
E. Milne ◽  
G. E. Lobley

The effect of abomasal infusion of glucose (120 kJ/d per kg body weight (BW)0·75, 758 mmol/d) on urea production, plasma alanine-N flux rate and the conversion of alanine-N to urea was studied in sheep offered a low-N diet at limited energy intake (500 kJ/d per kg BW0·75), based on hay and grass pellets. Glucose provision reduced urinary N (P= 0·040) and urea (P= 0·009) elimination but this was offset by poorer N digestibility. Urea-N production was significantly reduced (822v. 619 mmol/d,P= 0·024) by glucose while plasma alanine-N flux rate was elevated (295v. 342 mmol/d,P= 0·011). The quantity of urea-N derived from alanine tended to be decreased by glucose (127v. 95 mmol/d) but the fraction of urea production from alanine was unaltered (15 %). Plasma urea and alanine concentrations (plus those of the branched chain amino acids) decreased in response to exogenous glucose, an effect probably related to enhanced anabolic usage of amino acids and lowered urea production.


1986 ◽  
Vol 250 (4) ◽  
pp. E407-E413 ◽  
Author(s):  
R. A. Gelfand ◽  
M. G. Glickman ◽  
R. Jacob ◽  
R. S. Sherwin ◽  
R. A. DeFronzo

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.


1983 ◽  
Vol 244 (2) ◽  
pp. E151-E158 ◽  
Author(s):  
J. T. Brosnan ◽  
K. C. Man ◽  
D. E. Hall ◽  
S. A. Colbourne ◽  
M. E. Brosnan

Amino acid concentrations in whole blood, liver, kidney, skeletal muscle, and brain were measured and arteriovenous differences calculated for head, hindlimb, kidney, gut, and liver in control and streptozotocin-diabetic rats. In the control rats, glutamine was released by muscle and utilized by intestine, intestine released citrulline and alanine, liver removed alanine, and the kidneys removed glycine and produced serine. In diabetic rats, the major changes from the pattern of fluxes seen in the normal rat were the release of many amino acids from muscle, with glutamine and alanine predominating, and the uptake of these amino acids by the liver. Glutamine removal by the intestine was suppressed in diabetes, but a large renal uptake of glutamine was evident. Branched-chain amino acids were removed by the diabetic brain, and consequently, brain levels of a number of large neutral amino acids were decreased in diabetes.


2000 ◽  
Vol 118 (4) ◽  
pp. A774
Author(s):  
Honma Nobuko ◽  
Imagawa Yuriko ◽  
Kobayashi Tetsuo ◽  
Kadowaki Motoni ◽  
Takahashi Kazuyoshi

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