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Ghrelin Enhances in Vivo Skeletal Muscle But Not Liver AKT Signaling in Rats
Version of Record online: 6 SEP 2012
2007 North American Association for the Study of Obesity (NAASO)
Volume 15, Issue 11, pages 2614–2623, November 2007
How to Cite
Barazzoni, R., Zanetti, M., Cattin, M. R., Visintin, L., Vinci, P., Cattin, L., Stebel, M. and Guarnieri, G. (2007), Ghrelin Enhances in Vivo Skeletal Muscle But Not Liver AKT Signaling in Rats. Obesity, 15: 2614–2623. doi: 10.1038/oby.2007.313
- Issue online: 6 SEP 2012
- Version of Record online: 6 SEP 2012
- Received for review December 06, 2006, Accepted in final from February 26, 2007
- weight change
Objective: Ghrelin administration can induce fat weight gain and hyperglycemia (potentially through ghrelin-induced hepatic glucose production), but plasma ghrelin is positively associated with whole-body insulin sensitivity (mainly reflecting muscle insulin action) being increased in lean individuals or after diet-induced weight loss and reduced in obesity or after diet-induced weight gain. To investigate potential mechanisms, we measured in vivo effects of sustained ghrelin administration at a non-orexigenic dose on skeletal muscle and liver insulin signaling at the AKT level and adipokine expression changes.
Research Methods and Procedures: Young-adult male rats received 4-day, twice daily subcutaneous ghrelin (200 µg/injection) or saline. We measured skeletal muscle (mixed, gastrocnemius; oxidative, soleus) and liver protein levels of activated [phosphorylated (P)] and total (T) AKT and glycogen synthase kinase (GSK; reflecting AKT-dependent GSK inactivation) and epididymal adipose tissue adipokine mRNA.
Results: Ghrelin increased body weight (+1.4%) and blood glucose (both p < 0.05 vs. saline) but not food intake, plasma insulin, or free fatty acids. Ghrelin, however, enhanced P/T/AKT and P/T/GSK ratios and glucose transporter-4 mRNA in soleus (p < 0.05), but not in gastrocnemius, muscle. In contrast, ghrelin reduced hepatic P/T-AKT and P/T-GSK. No alterations occurred in adiponectin, leptin, or resistin transcripts or plasma adiponectin.
Discussion: Despite moderate weight gain and in the absence of insulin-free fatty acid changes, sustained ghrelin administration enhanced oxidative muscle AKT activation. Reduced liver AKT signaling could potentially contribute to concomitant blood glucose increments. These findings support ghrelin as a novel tissue-specific modulator of lean tissue AKT signaling with insulin-sensitizing effects in skeletal muscle but not in liver in vivo.