PAS kinase is required for normal cellular energy balance.
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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 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.
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| Authors | 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 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 39 Pg. 15466-71 (Sep 25 2007) ISSN: 0027-8424 [Print] United States |
| PMID | 17878307 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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