Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity

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Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. / Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H.

In: Cell Metabolism, Vol. 26, No. 4, 03.10.2017, p. 620-632.e6.

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

Harvard

Quarta, C, Clemmensen, C, Zhu, Z, Yang, B, Joseph, SS, Lutter, D, Yi, C-X, Graf, E, García-Cáceres, C, Legutko, B, Fischer, K, Brommage, R, Zizzari, P, Franklin, BS, Krueger, M, Koch, M, Vettorazzi, S, Li, P, Hofmann, SM, Bakhti, M, Bastidas-Ponce, A, Lickert, H, Strom, TM, Gailus-Durner, V, Bechmann, I, Perez-Tilve, D, Tuckermann, J, Hrabě de Angelis, M, Sandoval, D, Cota, D, Latz, E, Seeley, RJ, Müller, TD, DiMarchi, RD, Finan, B & Tschöp, MH 2017, 'Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity', Cell Metabolism, vol. 26, no. 4, pp. 620-632.e6. https://doi.org/10.1016/j.cmet.2017.08.023

APA

Quarta, C., Clemmensen, C., Zhu, Z., Yang, B., Joseph, S. S., Lutter, D., Yi, C-X., Graf, E., García-Cáceres, C., Legutko, B., Fischer, K., Brommage, R., Zizzari, P., Franklin, B. S., Krueger, M., Koch, M., Vettorazzi, S., Li, P., Hofmann, S. M., ... Tschöp, M. H. (2017). Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. Cell Metabolism, 26(4), 620-632.e6. https://doi.org/10.1016/j.cmet.2017.08.023

Vancouver

Quarta C, Clemmensen C, Zhu Z, Yang B, Joseph SS, Lutter D et al. Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. Cell Metabolism. 2017 Oct 3;26(4):620-632.e6. https://doi.org/10.1016/j.cmet.2017.08.023

Author

Quarta, Carmelo ; Clemmensen, Christoffer ; Zhu, Zhimeng ; Yang, Bin ; Joseph, Sini S ; Lutter, Dominik ; Yi, Chun-Xia ; Graf, Elisabeth ; García-Cáceres, Cristina ; Legutko, Beata ; Fischer, Katrin ; Brommage, Robert ; Zizzari, Philippe ; Franklin, Bernardo S ; Krueger, Martin ; Koch, Marco ; Vettorazzi, Sabine ; Li, Pengyun ; Hofmann, Susanna M ; Bakhti, Mostafa ; Bastidas-Ponce, Aimée ; Lickert, Heiko ; Strom, Tim M ; Gailus-Durner, Valerie ; Bechmann, Ingo ; Perez-Tilve, Diego ; Tuckermann, Jan ; Hrabě de Angelis, Martin ; Sandoval, Darleen ; Cota, Daniela ; Latz, Eicke ; Seeley, Randy J ; Müller, Timo D ; DiMarchi, Richard D ; Finan, Brian ; Tschöp, Matthias H. / Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. In: Cell Metabolism. 2017 ; Vol. 26, No. 4. pp. 620-632.e6.

Bibtex

@article{1f8a3b3ce93b416ab74da557a4f4d1a8,
title = "Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity",
abstract = "Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.",
keywords = "Journal Article",
author = "Carmelo Quarta and Christoffer Clemmensen and Zhimeng Zhu and Bin Yang and Joseph, {Sini S} and Dominik Lutter and Chun-Xia Yi and Elisabeth Graf and Cristina Garc{\'i}a-C{\'a}ceres and Beata Legutko and Katrin Fischer and Robert Brommage and Philippe Zizzari and Franklin, {Bernardo S} and Martin Krueger and Marco Koch and Sabine Vettorazzi and Pengyun Li and Hofmann, {Susanna M} and Mostafa Bakhti and Aim{\'e}e Bastidas-Ponce and Heiko Lickert and Strom, {Tim M} and Valerie Gailus-Durner and Ingo Bechmann and Diego Perez-Tilve and Jan Tuckermann and {Hrab{\v e} de Angelis}, Martin and Darleen Sandoval and Daniela Cota and Eicke Latz and Seeley, {Randy J} and M{\"u}ller, {Timo D} and DiMarchi, {Richard D} and Brian Finan and Tsch{\"o}p, {Matthias H}",
note = "Copyright {\textcopyright} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = oct,
day = "3",
doi = "10.1016/j.cmet.2017.08.023",
language = "English",
volume = "26",
pages = "620--632.e6",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity

AU - Quarta, Carmelo

AU - Clemmensen, Christoffer

AU - Zhu, Zhimeng

AU - Yang, Bin

AU - Joseph, Sini S

AU - Lutter, Dominik

AU - Yi, Chun-Xia

AU - Graf, Elisabeth

AU - García-Cáceres, Cristina

AU - Legutko, Beata

AU - Fischer, Katrin

AU - Brommage, Robert

AU - Zizzari, Philippe

AU - Franklin, Bernardo S

AU - Krueger, Martin

AU - Koch, Marco

AU - Vettorazzi, Sabine

AU - Li, Pengyun

AU - Hofmann, Susanna M

AU - Bakhti, Mostafa

AU - Bastidas-Ponce, Aimée

AU - Lickert, Heiko

AU - Strom, Tim M

AU - Gailus-Durner, Valerie

AU - Bechmann, Ingo

AU - Perez-Tilve, Diego

AU - Tuckermann, Jan

AU - Hrabě de Angelis, Martin

AU - Sandoval, Darleen

AU - Cota, Daniela

AU - Latz, Eicke

AU - Seeley, Randy J

AU - Müller, Timo D

AU - DiMarchi, Richard D

AU - Finan, Brian

AU - Tschöp, Matthias H

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/10/3

Y1 - 2017/10/3

N2 - Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.

AB - Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.

KW - Journal Article

U2 - 10.1016/j.cmet.2017.08.023

DO - 10.1016/j.cmet.2017.08.023

M3 - Journal article

C2 - 28943448

VL - 26

SP - 620-632.e6

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -

ID: 186639408