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A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

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Harvard

Maida, A, Zota, A, Sjøberg, KA, schumacher, J, Sijmonsma, T, Pfenninger, A, Christensen, MM, Gantert, T, Fuhrmeister, J, Rothermel, U, Schmoll, D, Heikenwälder, M, L. Iovanna, J, Stemmer, K, Kiens, B, Herzig, S & J. Rose, A 2016, 'A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution' The Journal of clinical investigation, vol. 126, no. 9.

APA

Maida, A., Zota, A., Sjøberg, K. A., schumacher, J., Sijmonsma, T., Pfenninger, A., ... J. Rose, A. (2016). A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. The Journal of clinical investigation, 126(9).

CBE

Maida A, Zota A, Sjøberg KA, schumacher J, Sijmonsma T, Pfenninger A, Christensen MM, Gantert T, Fuhrmeister J, Rothermel U, Schmoll D, Heikenwälder M, L. Iovanna J, Stemmer K, Kiens B, Herzig S, J. Rose A. 2016. A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. The Journal of clinical investigation. 126(9).

MLA

Vancouver

Maida A, Zota A, Sjøberg KA, schumacher J, Sijmonsma T, Pfenninger A et al. A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. The Journal of clinical investigation. 2016 Aug 22;126(9).

Author

Maida, Adriano ; Zota, Annika ; Sjøberg, Kim Anker ; schumacher, Jonas ; Sijmonsma, Tjeerd ; Pfenninger, Anja ; Christensen, Marie Møller ; Gantert, Thomas ; Fuhrmeister, Jessica ; Rothermel, Ulrike ; Schmoll, Dieter ; Heikenwälder, Mathias ; L. Iovanna, Juan ; Stemmer, Kerstin ; Kiens, Bente ; Herzig, Stephan ; J. Rose, Adam. / A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. In: The Journal of clinical investigation. 2016 ; Vol. 126, No. 9.

Bibtex

@article{39f6b382229d4e3fa70c791ce51d397b,
title = "A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution",
abstract = "Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21 expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response–driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency–induced liver NUPR1/FGF21 axis.",
keywords = "Health Sciences, Metabolism, Dietary Proteins, Insulin sensitivity, fgf21",
author = "Adriano Maida and Annika Zota and Sj{\o}berg, {Kim Anker} and Jonas schumacher and Tjeerd Sijmonsma and Anja Pfenninger and Christensen, {Marie M{\o}ller} and Thomas Gantert and Jessica Fuhrmeister and Ulrike Rothermel and Dieter Schmoll and Mathias Heikenw{\"a}lder and {L. Iovanna}, Juan and Kerstin Stemmer and Bente Kiens and Stephan Herzig and {J. Rose}, Adam",
year = "2016",
month = "8",
day = "22",
language = "English",
volume = "126",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "9",

}

RIS

TY - JOUR

T1 - A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

AU - Maida, Adriano

AU - Zota, Annika

AU - Sjøberg, Kim Anker

AU - schumacher, Jonas

AU - Sijmonsma, Tjeerd

AU - Pfenninger, Anja

AU - Christensen, Marie Møller

AU - Gantert, Thomas

AU - Fuhrmeister, Jessica

AU - Rothermel, Ulrike

AU - Schmoll, Dieter

AU - Heikenwälder, Mathias

AU - L. Iovanna, Juan

AU - Stemmer, Kerstin

AU - Kiens, Bente

AU - Herzig, Stephan

AU - J. Rose, Adam

PY - 2016/8/22

Y1 - 2016/8/22

N2 - Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21 expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response–driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency–induced liver NUPR1/FGF21 axis.

AB - Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21 expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response–driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency–induced liver NUPR1/FGF21 axis.

KW - Health Sciences

KW - Metabolism

KW - Dietary Proteins

KW - Insulin sensitivity

KW - fgf21

M3 - Journal article

VL - 126

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 9

ER -

ID: 53674391