Leucine

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Jose Donato - One of the best experts on this subject based on the ideXlab platform.

  • reviewing the effects of l Leucine supplementation in the regulation of food intake energy balance and glucose homeostasis
    Nutrients, 2015
    Co-Authors: Joao A B Pedroso, Thais T Zampieri, Jose Donato
    Abstract:

    Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). Because mTOR signaling regulates several aspects of metabolism, the potential of Leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of Leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central Leucine injection decreases food intake, this effect is not well reproduced when Leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral Leucine supplementation significantly affects food intake, although several studies have shown that Leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of Leucine supplementation in already-obese subjects. Finally, although several studies have found that Leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.

  • oral Leucine supplementation is sensed by the brain but neither reduces food intake nor induces an anorectic pattern of gene expression in the hypothalamus
    PLOS ONE, 2013
    Co-Authors: Thais T Zampieri, Joao A B Pedroso, Isadora C Furigo, Julio Tirapegui, Jose Donato
    Abstract:

    Leucine activates the intracellular mammalian target of the rapamycin (mTOR) pathway, and hypothalamic mTOR signaling regulates food intake. Although central infusion of Leucine reduces food intake, it is still uncertain whether oral Leucine supplementation is able to affect the hypothalamic circuits that control energy balance. We observed increased phosphorylation of p70s6k in the mouse hypothalamus after an acute oral gavage of Leucine. We then assessed whether acute oral gavage of Leucine induces the activation of neurons in several hypothalamic nuclei and in the brainstem. Leucine did not induce the expression of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive neurons in the area postrema. In addition, oral gavage of Leucine acutely increased the 24 h food intake of mice. Nonetheless, chronic Leucine supplementation in the drinking water did not change the food intake and the weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat diet. We assessed the hypothalamic gene expression and observed that Leucine supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK) that metabolize branched-chain amino acids. Despite these effects, Leucine supplementation did not induce an anorectic pattern of gene expression in the hypothalamus. In conclusion, our data show that the brain is able to sense oral Leucine intake. However, the food intake is not modified by chronic oral Leucine supplementation. These results question the possible efficacy of Leucine supplementation as an appetite suppressant to treat obesity.

Jimut Kanti Ghosh - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of Antimicrobial, Cytotoxic, and Antiendotoxin Properties of Short Peptides with Different Hydrophobic Amino Acids at “a” and “d” Positions of a Heptad Repeat Sequence
    2016
    Co-Authors: Sarfuddin Azmi, Saurabh Srivastava, Nripendra N. Mishra, Jitendra K. Tripathi, Praveen K. Shukla, Jimut Kanti Ghosh
    Abstract:

    To understand the influence of different hydrophobic amino acids at “a” and “d” positions of a heptad repeat sequence on antimicrobial, cytotoxic, and antiendotoxin properties, four 15-residue peptides with Leucine (LRP), phenylalanine (FRP), valine (VRP), and alanine (ARP) residues at these positions were designed, synthesized, and characterized. Although valine is similarly hydrophobic to Leucine and phenylalanine, VRP showed significantly lesser cytotoxicity than LRP and FRP; further, the replacement of Leucines with valines at “a” and “d” positions of melittin-heptads drastically reduced its cytotoxicity. However, all four peptides exhibited significant antimicrobial activities that correlate well with their interactions with mammalian and bacterial cell membranes and the corresponding lipid vesicles. LRP most efficiently neutralized the LPS-induced pro-inflammatory mediators like NO, TNF-α, and IL-6 in macrophages followed by FRP, VRP, and ARP. The results could be useful for designing short antimicrobial and antiendotoxin peptides with understanding the basis of their activity

  • characterization of antimicrobial cytotoxic and antiendotoxin properties of short peptides with different hydrophobic amino acids at a and d positions of a heptad repeat sequence
    Journal of Medicinal Chemistry, 2013
    Co-Authors: Sarfuddin Azmi, Saurabh Srivastava, Nripendra N. Mishra, Jitendra K. Tripathi, Praveen K. Shukla, Jimut Kanti Ghosh
    Abstract:

    To understand the influence of different hydrophobic amino acids at “a” and “d” positions of a heptad repeat sequence on antimicrobial, cytotoxic, and antiendotoxin properties, four 15-residue peptides with Leucine (LRP), phenylalanine (FRP), valine (VRP), and alanine (ARP) residues at these positions were designed, synthesized, and characterized. Although valine is similarly hydrophobic to Leucine and phenylalanine, VRP showed significantly lesser cytotoxicity than LRP and FRP; further, the replacement of Leucines with valines at “a” and “d” positions of melittin-heptads drastically reduced its cytotoxicity. However, all four peptides exhibited significant antimicrobial activities that correlate well with their interactions with mammalian and bacterial cell membranes and the corresponding lipid vesicles. LRP most efficiently neutralized the LPS-induced pro-inflammatory mediators like NO, TNF-α, and IL-6 in macrophages followed by FRP, VRP, and ARP. The results could be useful for designing short antimicr...

Thais T Zampieri - One of the best experts on this subject based on the ideXlab platform.

  • reviewing the effects of l Leucine supplementation in the regulation of food intake energy balance and glucose homeostasis
    Nutrients, 2015
    Co-Authors: Joao A B Pedroso, Thais T Zampieri, Jose Donato
    Abstract:

    Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). Because mTOR signaling regulates several aspects of metabolism, the potential of Leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of Leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central Leucine injection decreases food intake, this effect is not well reproduced when Leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral Leucine supplementation significantly affects food intake, although several studies have shown that Leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of Leucine supplementation in already-obese subjects. Finally, although several studies have found that Leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.

  • oral Leucine supplementation is sensed by the brain but neither reduces food intake nor induces an anorectic pattern of gene expression in the hypothalamus
    PLOS ONE, 2013
    Co-Authors: Thais T Zampieri, Joao A B Pedroso, Isadora C Furigo, Julio Tirapegui, Jose Donato
    Abstract:

    Leucine activates the intracellular mammalian target of the rapamycin (mTOR) pathway, and hypothalamic mTOR signaling regulates food intake. Although central infusion of Leucine reduces food intake, it is still uncertain whether oral Leucine supplementation is able to affect the hypothalamic circuits that control energy balance. We observed increased phosphorylation of p70s6k in the mouse hypothalamus after an acute oral gavage of Leucine. We then assessed whether acute oral gavage of Leucine induces the activation of neurons in several hypothalamic nuclei and in the brainstem. Leucine did not induce the expression of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive neurons in the area postrema. In addition, oral gavage of Leucine acutely increased the 24 h food intake of mice. Nonetheless, chronic Leucine supplementation in the drinking water did not change the food intake and the weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat diet. We assessed the hypothalamic gene expression and observed that Leucine supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK) that metabolize branched-chain amino acids. Despite these effects, Leucine supplementation did not induce an anorectic pattern of gene expression in the hypothalamus. In conclusion, our data show that the brain is able to sense oral Leucine intake. However, the food intake is not modified by chronic oral Leucine supplementation. These results question the possible efficacy of Leucine supplementation as an appetite suppressant to treat obesity.

Joao A B Pedroso - One of the best experts on this subject based on the ideXlab platform.

  • reviewing the effects of l Leucine supplementation in the regulation of food intake energy balance and glucose homeostasis
    Nutrients, 2015
    Co-Authors: Joao A B Pedroso, Thais T Zampieri, Jose Donato
    Abstract:

    Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). Because mTOR signaling regulates several aspects of metabolism, the potential of Leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of Leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central Leucine injection decreases food intake, this effect is not well reproduced when Leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral Leucine supplementation significantly affects food intake, although several studies have shown that Leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of Leucine supplementation in already-obese subjects. Finally, although several studies have found that Leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.

  • oral Leucine supplementation is sensed by the brain but neither reduces food intake nor induces an anorectic pattern of gene expression in the hypothalamus
    PLOS ONE, 2013
    Co-Authors: Thais T Zampieri, Joao A B Pedroso, Isadora C Furigo, Julio Tirapegui, Jose Donato
    Abstract:

    Leucine activates the intracellular mammalian target of the rapamycin (mTOR) pathway, and hypothalamic mTOR signaling regulates food intake. Although central infusion of Leucine reduces food intake, it is still uncertain whether oral Leucine supplementation is able to affect the hypothalamic circuits that control energy balance. We observed increased phosphorylation of p70s6k in the mouse hypothalamus after an acute oral gavage of Leucine. We then assessed whether acute oral gavage of Leucine induces the activation of neurons in several hypothalamic nuclei and in the brainstem. Leucine did not induce the expression of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive neurons in the area postrema. In addition, oral gavage of Leucine acutely increased the 24 h food intake of mice. Nonetheless, chronic Leucine supplementation in the drinking water did not change the food intake and the weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat diet. We assessed the hypothalamic gene expression and observed that Leucine supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK) that metabolize branched-chain amino acids. Despite these effects, Leucine supplementation did not induce an anorectic pattern of gene expression in the hypothalamus. In conclusion, our data show that the brain is able to sense oral Leucine intake. However, the food intake is not modified by chronic oral Leucine supplementation. These results question the possible efficacy of Leucine supplementation as an appetite suppressant to treat obesity.

Michel Krempf - One of the best experts on this subject based on the ideXlab platform.

  • hyperglucagonemia and the immediate fate of dietary Leucine a kinetic study in humans
    Metabolism-clinical and Experimental, 1998
    Co-Authors: Sergio J Marchini, Lisa Marks, Dominique Darmaun, Vernon R Young, Michel Krempf
    Abstract:

    Abstract The possible role of glucagon in determining the fate of dietary absorbed amino acids within the splanchnic bed was investigated in five healthy male volunteers. A kinetic study was performed involving a continuous 240-minute infusion of l-[5,5,5- 2 H 3 ]Leucine and d-[6,6- 2 H 2 ]glucose by vein, while l-[1- 13 C]Leucine was infused by a feeding tube into the duodenum (intragut [IG]) along with a constant intravenous (IV) infusion of somatotropin release-inhibitory factor (SRIF) combined with insulin, growth hormone, and glucagon. In random order, glucagon was infused at a rate of 0.4 ng · kg −1 · min −1 in one experiment and 1.2 ng · kg −1 · min −1 in the other experiment, while insulin and growth hormone were kept at constant serum levels, respectively, 37 ± 13 pmol · L −1 and 5 ± 0.2 μg · L −1 . The diet was provided as an l-amino acid solution including 60 μmol · kg −1 · h −1 Leucine without fat and carbohydrate. During the higher rate of glucagon infusion, there was an increase in plasma glucagon and glucose concentrations, glucose flux, and net dietary Leucine release into the periphery from the splanchnic bed. Splanchnic removal and uptake of Leucine were decreased with increased glucagon infusion. There were no statistical differences in the plasma Leucine level and IV and IG Leucine fluxes at the two glucagon levels, although Leucine metabolic clearance increased (0.74 v 0.85 L · kg −1 · h −1 , P = .08) in the case of glucagon excess. Plasma glucose increased with glucagon excess and was negatively correlated ( P r = −.348) and IV ( r = −.459) or I.G. ( r = −.359) Leucine fluxes. The negative correlation between plasma glucagon and Leucine levels was also significant ( r = −.684). No significant correlation was found between dietary Leucine splanchnic removal and glucose, glucagon, or Leucine plasma concentrations. We conclude that glucagon in excess has only a small quantitative effect on the overall handling of dietary Leucine, and hypothesize that more Leucine is exported to the peripheral tissues under these hormonal conditions.