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

作者：Enns Linda C; Morton John F; Mangalindan Ruby Sue; McKnight G Stanley; Schwartz Michael W; Kaeberlein Matt R; Kennedy Brian K; Rabinovitch Peter S; Ladiges Warren C^*

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2009, 64(12): 1221-1231.

DOI：10.1093/gerona/glp133

• Aging
• PKA C beta
• Metabolic syndrome
• Obesity resistance
• Insulin sensitivity

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 C beta. We confirmed that C beta has high levels of expression in the brain but also showed moderate levels in liver. C beta-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of C beta 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.

• 出版日期2009-12