Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance

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

Standard

Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance. / Nelson, Marin E; Madsen, Søren; Cooke, Kristen C; Fritzen, Andreas Mæchel; Thorius, Ida H; Masson, Stewart W C; Carroll, Luke; Weiss, Fiona C; Seldin, Marcus M; Potter, Meg; Hocking, Samantha L; Fazakerley, Daniel J; Brandon, Amanda E; Thillainadesan, Senthil; Senior, Alistair M; Cooney, Gregory J; Stöckli, Jacqueline; James, David E.

In: Cell Metabolism, Vol. 34, No. 2, 2022, p. 227-239.e6.

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

Harvard

Nelson, ME, Madsen, S, Cooke, KC, Fritzen, AM, Thorius, IH, Masson, SWC, Carroll, L, Weiss, FC, Seldin, MM, Potter, M, Hocking, SL, Fazakerley, DJ, Brandon, AE, Thillainadesan, S, Senior, AM, Cooney, GJ, Stöckli, J & James, DE 2022, 'Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance', Cell Metabolism, vol. 34, no. 2, pp. 227-239.e6. https://doi.org/10.1016/j.cmet.2021.12.013

APA

Nelson, M. E., Madsen, S., Cooke, K. C., Fritzen, A. M., Thorius, I. H., Masson, S. W. C., Carroll, L., Weiss, F. C., Seldin, M. M., Potter, M., Hocking, S. L., Fazakerley, D. J., Brandon, A. E., Thillainadesan, S., Senior, A. M., Cooney, G. J., Stöckli, J., & James, D. E. (2022). Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance. Cell Metabolism, 34(2), 227-239.e6. https://doi.org/10.1016/j.cmet.2021.12.013

Vancouver

Nelson ME, Madsen S, Cooke KC, Fritzen AM, Thorius IH, Masson SWC et al. Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance. Cell Metabolism. 2022;34(2):227-239.e6. https://doi.org/10.1016/j.cmet.2021.12.013

Author

Nelson, Marin E ; Madsen, Søren ; Cooke, Kristen C ; Fritzen, Andreas Mæchel ; Thorius, Ida H ; Masson, Stewart W C ; Carroll, Luke ; Weiss, Fiona C ; Seldin, Marcus M ; Potter, Meg ; Hocking, Samantha L ; Fazakerley, Daniel J ; Brandon, Amanda E ; Thillainadesan, Senthil ; Senior, Alistair M ; Cooney, Gregory J ; Stöckli, Jacqueline ; James, David E. / Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance. In: Cell Metabolism. 2022 ; Vol. 34, No. 2. pp. 227-239.e6.

Bibtex

@article{f3f6b97aac674c50badc519704bb22c5,

title = "Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance",

abstract = "Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.",

author = "Nelson, {Marin E} and S{\o}ren Madsen and Cooke, {Kristen C} and Fritzen, {Andreas M{\ae}chel} and Thorius, {Ida H} and Masson, {Stewart W C} and Luke Carroll and Weiss, {Fiona C} and Seldin, {Marcus M} and Meg Potter and Hocking, {Samantha L} and Fazakerley, {Daniel J} and Brandon, {Amanda E} and Senthil Thillainadesan and Senior, {Alistair M} and Cooney, {Gregory J} and Jacqueline St{\"o}ckli and James, {David E}",

year = "2022",

doi = "10.1016/j.cmet.2021.12.013",

language = "English",

volume = "34",

pages = "227--239.e6",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "2",

}

RIS

TY - JOUR

T1 - Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance

AU - Nelson, Marin E

AU - Madsen, Søren

AU - Cooke, Kristen C

AU - Fritzen, Andreas Mæchel

AU - Thorius, Ida H

AU - Masson, Stewart W C

AU - Carroll, Luke

AU - Weiss, Fiona C

AU - Seldin, Marcus M

AU - Potter, Meg

AU - Hocking, Samantha L

AU - Fazakerley, Daniel J

AU - Brandon, Amanda E

AU - Thillainadesan, Senthil

AU - Senior, Alistair M

AU - Cooney, Gregory J

AU - Stöckli, Jacqueline

AU - James, David E

PY - 2022

Y1 - 2022

N2 - Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.

AB - Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.

U2 - 10.1016/j.cmet.2021.12.013

DO - 10.1016/j.cmet.2021.12.013

M3 - Journal article

C2 - 35021042

VL - 34

SP - 227-239.e6

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 2

ER -

ID: 289453295

Department of Biomedical Sciences