Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice

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Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. / Zachariah Tom, Robby; Garcia-Roves, Pablo M; Sjögren, Rasmus J O; Jiang, Lake Q; Holmström, Maria H; Deshmukh, Atul S; Vieira, Elaine; Chibalin, Alexander V; Björnholm, Marie; Zierath, Juleen R.

In: Diabetes, Vol. 63, No. 5, 05.2014, p. 1560-71.

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

Harvard

Zachariah Tom, R, Garcia-Roves, PM, Sjögren, RJO, Jiang, LQ, Holmström, MH, Deshmukh, AS, Vieira, E, Chibalin, AV, Björnholm, M & Zierath, JR 2014, 'Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice', Diabetes, vol. 63, no. 5, pp. 1560-71. https://doi.org/10.2337/db13-0670

APA

Zachariah Tom, R., Garcia-Roves, P. M., Sjögren, R. J. O., Jiang, L. Q., Holmström, M. H., Deshmukh, A. S., Vieira, E., Chibalin, A. V., Björnholm, M., & Zierath, J. R. (2014). Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes, 63(5), 1560-71. https://doi.org/10.2337/db13-0670

Vancouver

Zachariah Tom R, Garcia-Roves PM, Sjögren RJO, Jiang LQ, Holmström MH, Deshmukh AS et al. Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes. 2014 May;63(5):1560-71. https://doi.org/10.2337/db13-0670

Author

Zachariah Tom, Robby ; Garcia-Roves, Pablo M ; Sjögren, Rasmus J O ; Jiang, Lake Q ; Holmström, Maria H ; Deshmukh, Atul S ; Vieira, Elaine ; Chibalin, Alexander V ; Björnholm, Marie ; Zierath, Juleen R. / Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. In: Diabetes. 2014 ; Vol. 63, No. 5. pp. 1560-71.

Bibtex

@article{4d5fa5318bcf4cb4ac543cad489a4b9b,
title = "Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice",
abstract = "AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation. ",
keywords = "Acetyl-CoA Carboxylase/metabolism, Adenylate Kinase/metabolism, Animals, Female, Glucagon/metabolism, Insulin/metabolism, Insulin Resistance/physiology, Leptin/genetics, Lipid Metabolism, Male, Mice, Mice, Obese, Muscle, Skeletal/drug effects, Obesity/metabolism, Phosphorylation/drug effects",
author = "{Zachariah Tom}, Robby and Garcia-Roves, {Pablo M} and Sj{\"o}gren, {Rasmus J O} and Jiang, {Lake Q} and Holmstr{\"o}m, {Maria H} and Deshmukh, {Atul S} and Elaine Vieira and Chibalin, {Alexander V} and Marie Bj{\"o}rnholm and Zierath, {Juleen R}",
year = "2014",
month = may,
doi = "10.2337/db13-0670",
language = "English",
volume = "63",
pages = "1560--71",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "5",

}

RIS

TY - JOUR

T1 - Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice

AU - Zachariah Tom, Robby

AU - Garcia-Roves, Pablo M

AU - Sjögren, Rasmus J O

AU - Jiang, Lake Q

AU - Holmström, Maria H

AU - Deshmukh, Atul S

AU - Vieira, Elaine

AU - Chibalin, Alexander V

AU - Björnholm, Marie

AU - Zierath, Juleen R

PY - 2014/5

Y1 - 2014/5

N2 - AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation.

AB - AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKγ3(R225Q) mutation.

KW - Acetyl-CoA Carboxylase/metabolism

KW - Adenylate Kinase/metabolism

KW - Animals

KW - Female

KW - Glucagon/metabolism

KW - Insulin/metabolism

KW - Insulin Resistance/physiology

KW - Leptin/genetics

KW - Lipid Metabolism

KW - Male

KW - Mice

KW - Mice, Obese

KW - Muscle, Skeletal/drug effects

KW - Obesity/metabolism

KW - Phosphorylation/drug effects

U2 - 10.2337/db13-0670

DO - 10.2337/db13-0670

M3 - Journal article

C2 - 24487023

VL - 63

SP - 1560

EP - 1571

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -

ID: 218626868