PAS kinase is required for normal cellular energy balance

Huai-Xiang Hao; Caleb M Cardon; Wojtek Swiatek; Robert C Cooksey; Tammy L Smith; James Wilde; Sihem Boudina; E. Dale Abel; Donald A McClain; Jared Rutter

doi:10.1073/pnas.0705407104

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PAS kinase is required for normal cellular energy balance

Journal article

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PAS kinase is required for normal cellular energy balance

Huai-Xiang Hao, Caleb M Cardon, Wojtek Swiatek, Robert C Cooksey, Tammy L Smith, James Wilde, Sihem Boudina, E. Dale Abel, Donald A McClain and Jared Rutter

Proceedings of the National Academy of Sciences - PNAS, Vol.104(39), pp.15466-15471

09/25/2007

DOI: 10.1073/pnas.0705407104

PMCID: PMC2000499

PMID: 17878307

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Abstract

The metabolic syndrome, a complex set of phenotypes typically associated with obesity and diabetes, is an increasing threat to global public health. Fundamentally, the metabolic syndrome is caused by a failure to properly sense and respond to cellular metabolic cues. We studied the role of the cellular metabolic sensor PAS kinase (PASK) in the pathogenesis of metabolic disease by using PASK −/− mice. We identified tissue-specific metabolic phenotypes caused by PASK deletion consistent with its role as a metabolic sensor. Specifically, PASK −/− mice exhibited impaired glucose-stimulated insulin secretion in pancreatic β-cells, altered triglyceride storage in liver, and increased metabolic rate in skeletal muscle. Further, PASK deletion caused nearly complete protection from the deleterious effects of a high-fat diet including obesity and insulin resistance. We also demonstrate that these cellular effects, increased rate of oxidative metabolism and ATP production, occur in cultured cells. We therefore hypothesize that PASK acts in a cell-autonomous manner to maintain cellular energy homeostasis and is a potential therapeutic target for metabolic disease.

Biological Sciences

PAS domain

metabolism

obesity

nutrient sensing

Details

Title: Subtitle: PAS kinase is required for normal cellular energy balance
Creators: Huai-Xiang Hao - Department of Biochemistry and
Caleb M Cardon - Department of Biochemistry and
Wojtek Swiatek - Department of Biochemistry and
Robert C Cooksey - Division of Endocrinology, Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112
Tammy L Smith - Department of Biochemistry and
James Wilde - Department of Biochemistry and
Sihem Boudina - Division of Endocrinology, Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112
E. Dale Abel - Division of Endocrinology, Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112
Donald A McClain - Division of Endocrinology, Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112
Jared Rutter - Department of Biochemistry and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.104(39), pp.15466-15471
DOI: 10.1073/pnas.0705407104
PMID: 17878307
PMCID: PMC2000499
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 09/25/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024420902771

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