期刊
OBESITY
卷 15, 期 11, 页码 2614-2623出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/oby.2007.313
关键词
ghrelin; adipokines; 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 mu g/ 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 (1) < 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 sup, port 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.
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