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Ghrelin Enhances in Vivo Skeletal Muscle But Not Liver AKT Signaling in Rats
Author(s) -
Barazzoni Rocco,
Zanetti Michela,
Cattin Maria Rosa,
Visintin Luca,
Vinci Pierandrea,
Cattin Luigi,
Stebel Marco,
Guarnieri Gianfranco
Publication year - 2007
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2007.313
Subject(s) - endocrinology , medicine , ghrelin , adipokine , protein kinase b , insulin , adiponectin , leptin , resistin , skeletal muscle , adipose tissue , insulin resistance , chemistry , phosphorylation , obesity , hormone , biochemistry
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.