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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access originally published online on September 23, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2009 64A(12):1221-1231; doi:10.1093/gerona/glp133
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Attenuation of Age-Related Metabolic Dysfunction in Mice With a Targeted Disruption of the Cβ Subunit of Protein Kinase A

Linda C. Enns1, John F. Morton1, Ruby Sue Mangalindan1, G. Stanley McKnight2, Michael W. Schwartz3, Matt R. Kaeberlein4, Brian K. Kennedy5, Peter S. Rabinovitch4 and Warren C. Ladiges1

1 Department of Comparative Medicine
2 Department of Pharmacology
3 Department of Medicine
4 Department of Pathology
5 Department of Biochemistry, University of Washington, Seattle

Address correspondence to Warren C. Ladiges, D.V.M, M.S., Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, 98915. Email: Wladiges{at}u.washington.edu


  Abstract

The cyclic adenosine monophosphate–dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cβ. We confirmed that Cβ has high levels of expression in the brain but also showed moderate levels in liver. Cβ-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cβ protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance.

Keywords Aging; PKA Cβ; Metabolic syndrome; Obesity resistance; Insulin sensitivity

Received: February 4, 2009; Accepted: August 25, 2009

Decision Editor: Huber R. Warner, PhD


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