Research ExplorerPublicationsBrain insulin lowers circulating BCAA levels by inducing hep...

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

Standard

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. / Shin, Andrew C; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J; Lapworth, Amanda L; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M; Scheja, Ludger; Grove, Kevin L; Smith, Richard D; Qian, Wei-Jun; Lynch, Christopher J; Newgard, Christopher B; Buettner, Christoph.

In: CELL METAB, Vol. 20, No. 5, 04.11.2014, p. 898-909.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Shin, AC, Fasshauer, M, Filatova, N, Grundell, LA, Zielinski, E, Zhou, J-Y, Scherer, T, Lindtner, C, White, PJ, Lapworth, AL, Ilkayeva, O, Knippschild, U, Wolf, AM, Scheja, L, Grove, KL, Smith, RD, Qian, W-J, Lynch, CJ, Newgard, CB & Buettner, C 2014, 'Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism', CELL METAB, vol. 20, no. 5, pp. 898-909. https://doi.org/10.1016/j.cmet.2014.09.003

APA

Shin, A. C., Fasshauer, M., Filatova, N., Grundell, L. A., Zielinski, E., Zhou, J-Y., Scherer, T., Lindtner, C., White, P. J., Lapworth, A. L., Ilkayeva, O., Knippschild, U., Wolf, A. M., Scheja, L., Grove, K. L., Smith, R. D., Qian, W-J., Lynch, C. J., Newgard, C. B., & Buettner, C. (2014). Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. CELL METAB, 20(5), 898-909. https://doi.org/10.1016/j.cmet.2014.09.003

Vancouver

Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou J-Y et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. CELL METAB. 2014 Nov 4;20(5):898-909. https://doi.org/10.1016/j.cmet.2014.09.003

Bibtex

@article{8eea6f61802649559cecc51a4b8abe78,
title = "Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism",
abstract = "Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.",
author = "Shin, {Andrew C} and Martin Fasshauer and Nika Filatova and Grundell, {Linus A} and Elizabeth Zielinski and Jian-Ying Zhou and Thomas Scherer and Claudia Lindtner and White, {Phillip J} and Lapworth, {Amanda L} and Olga Ilkayeva and Uwe Knippschild and Wolf, {Anna M} and Ludger Scheja and Grove, {Kevin L} and Smith, {Richard D} and Wei-Jun Qian and Lynch, {Christopher J} and Newgard, {Christopher B} and Christoph Buettner",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = nov,
day = "4",
doi = "10.1016/j.cmet.2014.09.003",
language = "English",
volume = "20",
pages = "898--909",
journal = "CELL METAB",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

AU - Shin, Andrew C

AU - Fasshauer, Martin

AU - Filatova, Nika

AU - Grundell, Linus A

AU - Zielinski, Elizabeth

AU - Zhou, Jian-Ying

AU - Scherer, Thomas

AU - Lindtner, Claudia

AU - White, Phillip J

AU - Lapworth, Amanda L

AU - Ilkayeva, Olga

AU - Knippschild, Uwe

AU - Wolf, Anna M

AU - Scheja, Ludger

AU - Grove, Kevin L

AU - Smith, Richard D

AU - Qian, Wei-Jun

AU - Lynch, Christopher J

AU - Newgard, Christopher B

AU - Buettner, Christoph

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/11/4

Y1 - 2014/11/4

N2 - Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

AB - Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

U2 - 10.1016/j.cmet.2014.09.003

DO - 10.1016/j.cmet.2014.09.003

M3 - SCORING: Journal article

C2 - 25307860

VL - 20

SP - 898

EP - 909

JO - CELL METAB

JF - CELL METAB

SN - 1550-4131

IS - 5

ER -