Effects of excess corticosterone on LKB1 and AMPK signaling in rat skeletal muscle

• Published in: Journal of applied physiology (1985) 2010-02, Vol.108 (2), p.298-305
• Main Authors: Nakken, G. Nathan, Jacobs, Daniel L, Thomson, David M, Fillmore, Natasha, Winder, William W
• Format: Article
• Language: English
• Subjects: Adrenal Glands - pathology; Animals; Atrophy; Blotting, Western; Body Weight - drug effects; Comparative analysis; Corticosterone - pharmacology; Corticosterone - toxicity; Cyclic AMP-Dependent Protein Kinases - physiology; Effects; Electric Stimulation; Hormones; Immunoprecipitation; Insulin - blood; Insulin Resistance; Isoenzymes - biosynthesis; Isoenzymes - genetics; Kinases; Leptin - blood; Lipid Metabolism - drug effects; Male; Muscle Contraction - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Muscle, Skeletal - pathology; Musculoskeletal system; Plasma; Protein-Serine-Threonine Kinases - physiology; Proteins - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction - drug effects
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00906.2009

Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah Submitted 12 August 2009 ; accepted in final form 29 November 2009 Cushing's syndrome is characterized by marked central obesity and insulin insensitivity, effects opposite those seen with chronic AMP-activated protein kinase (AMPK) activation. This study was designed to determine whether chronic exposure to excess glucocorticoids influences LKB1/AMPK signaling in skeletal muscle. Corticosterone pellets were implanted subcutaneously in rats (hypercorticosteronemia, Hypercort) for 2 wk. Controls were sham operated and fed ad libitum or were sham operated and food restricted (pair-weighted group, Pair) to produce body weights similar to Hypercort rats. At the end of the 2-wk treatment period, rats were anesthetized, and the right gastrocnemius-plantaris (gastroc) and soleus muscles were removed. Left muscles were removed after electrical stimulation for 5 min. No significant differences were noted between treatment groups in ATP, creatine phosphate, or LKB1 activity. The - and β-subunit isoforms were not significantly influenced in gastroc by corticosterone treatment. Expression of the 3-subunit decreased, and 1- and 2-subunit expression increased. Both 2-AMPK and 1-AMPK activities were increased in the gastroc in response to electrical stimulation, but the magnitude of the increase was less for 2 in the Hypercort rats. Despite elevated plasma insulin and elevated plasma leptin in the Hypercort rats, phosphorylation of TBC1D1 was lower in both resting and stimulated muscle compared with controls. Malonyl-CoA content was elevated in gastroc muscles of resting Hypercort rats. These changes in response to excess glucocorticoids could be responsible, in part, for the decrease in insulin sensitivity and adiposity seen in Cushing's syndrome. Cushing's syndrome; glucocorticoids Address for reprint requests and other correspondence: W. W. Winder, Dept. of Physiology and Developmental Biology, 575 WIDB, Brigham Young Univ., Provo, Utah 84602 (e-mail: William_winder{at}byu.edu )