Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice

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Standard

Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice. / Jall, Sigrid; Sachs, Stephan; Clemmensen, Christoffer; Finan, Brian; Neff, Frauke; DiMarchi, Richard D; Tschöp, Matthias H; Müller, Timo D; Hofmann, Susanna M.

I: Molecular Metabolism, Bind 6, Nr. 5, 05.2017, s. 440-446.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Jall, S, Sachs, S, Clemmensen, C, Finan, B, Neff, F, DiMarchi, RD, Tschöp, MH, Müller, TD & Hofmann, SM 2017, 'Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice', Molecular Metabolism, bind 6, nr. 5, s. 440-446. https://doi.org/10.1016/j.molmet.2017.02.002

APA

Jall, S., Sachs, S., Clemmensen, C., Finan, B., Neff, F., DiMarchi, R. D., Tschöp, M. H., Müller, T. D., & Hofmann, S. M. (2017). Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice. Molecular Metabolism, 6(5), 440-446. https://doi.org/10.1016/j.molmet.2017.02.002

Vancouver

Jall S, Sachs S, Clemmensen C, Finan B, Neff F, DiMarchi RD o.a. Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice. Molecular Metabolism. 2017 maj;6(5):440-446. https://doi.org/10.1016/j.molmet.2017.02.002

Author

Jall, Sigrid ; Sachs, Stephan ; Clemmensen, Christoffer ; Finan, Brian ; Neff, Frauke ; DiMarchi, Richard D ; Tschöp, Matthias H ; Müller, Timo D ; Hofmann, Susanna M. / Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice. I: Molecular Metabolism. 2017 ; Bind 6, Nr. 5. s. 440-446.

Bibtex

@article{7d55f4474143411c997a71785d78f531,
title = "Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice",
abstract = "OBJECTIVE: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice.METHODS: Female C57BL/6J mice and a cohort of fatmass-matched C57BL/6J male mice were treated for 27 days via subcutaneous injections with either the GLP-1/GIP/glucagon triagonist or PBS. A second cohort of C57BL/6J male mice was included to match the females in the duration of the high-fat, high-sugar diet (HFD) exposure.RESULTS: Our results show that GLP-1/GIP/glucagon triple agonism inhibits food intake and decreases body weight and body fat mass with comparable potency in male and female mice that have been matched for body fat mass. Treatment improved dyslipidemia in both sexes and reversed diet-induced steatohepatitis to a larger extent in female mice compared to male mice.CONCLUSIONS: We herein show that a recently developed unimolecular peptide triagonist is equally efficient in both sexes, suggesting that this polypharmaceutical strategy might be a relevant alternative to bariatric surgery for the treatment of obesity and related metabolic disorders.",
keywords = "Journal Article",
author = "Sigrid Jall and Stephan Sachs and Christoffer Clemmensen and Brian Finan and Frauke Neff and DiMarchi, {Richard D} and Tsch{\"o}p, {Matthias H} and M{\"u}ller, {Timo D} and Hofmann, {Susanna M}",
year = "2017",
month = may,
doi = "10.1016/j.molmet.2017.02.002",
language = "English",
volume = "6",
pages = "440--446",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice

AU - Jall, Sigrid

AU - Sachs, Stephan

AU - Clemmensen, Christoffer

AU - Finan, Brian

AU - Neff, Frauke

AU - DiMarchi, Richard D

AU - Tschöp, Matthias H

AU - Müller, Timo D

AU - Hofmann, Susanna M

PY - 2017/5

Y1 - 2017/5

N2 - OBJECTIVE: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice.METHODS: Female C57BL/6J mice and a cohort of fatmass-matched C57BL/6J male mice were treated for 27 days via subcutaneous injections with either the GLP-1/GIP/glucagon triagonist or PBS. A second cohort of C57BL/6J male mice was included to match the females in the duration of the high-fat, high-sugar diet (HFD) exposure.RESULTS: Our results show that GLP-1/GIP/glucagon triple agonism inhibits food intake and decreases body weight and body fat mass with comparable potency in male and female mice that have been matched for body fat mass. Treatment improved dyslipidemia in both sexes and reversed diet-induced steatohepatitis to a larger extent in female mice compared to male mice.CONCLUSIONS: We herein show that a recently developed unimolecular peptide triagonist is equally efficient in both sexes, suggesting that this polypharmaceutical strategy might be a relevant alternative to bariatric surgery for the treatment of obesity and related metabolic disorders.

AB - OBJECTIVE: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice.METHODS: Female C57BL/6J mice and a cohort of fatmass-matched C57BL/6J male mice were treated for 27 days via subcutaneous injections with either the GLP-1/GIP/glucagon triagonist or PBS. A second cohort of C57BL/6J male mice was included to match the females in the duration of the high-fat, high-sugar diet (HFD) exposure.RESULTS: Our results show that GLP-1/GIP/glucagon triple agonism inhibits food intake and decreases body weight and body fat mass with comparable potency in male and female mice that have been matched for body fat mass. Treatment improved dyslipidemia in both sexes and reversed diet-induced steatohepatitis to a larger extent in female mice compared to male mice.CONCLUSIONS: We herein show that a recently developed unimolecular peptide triagonist is equally efficient in both sexes, suggesting that this polypharmaceutical strategy might be a relevant alternative to bariatric surgery for the treatment of obesity and related metabolic disorders.

KW - Journal Article

U2 - 10.1016/j.molmet.2017.02.002

DO - 10.1016/j.molmet.2017.02.002

M3 - Journal article

C2 - 28462078

VL - 6

SP - 440

EP - 446

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

IS - 5

ER -

ID: 186639533