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PAS kinase is required for normal cellular energy balance.


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 beta-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.

SUBMITTER: Hao HX 

PROVIDER: S-EPMC2000499 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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PAS kinase is required for normal cellular energy balance.

Hao Huai-Xiang HX   Cardon Caleb M CM   Swiatek Wojtek W   Cooksey Robert C RC   Smith Tammy L TL   Wilde James J   Boudina Sihem S   Abel E Dale ED   McClain Donald A DA   Rutter Jared J  

Proceedings of the National Academy of Sciences of the United States of America 20070918 39


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  ...[more]

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