From Feast to Famine: A Tale of Satiety and Hunger Hormones




Zhang, Yuanyuan

Journal Title

Journal ISSN

Volume Title


Content Notes


Ghrelin is a peptide hormone secreted mainly from the stomach. It has a unique octanoylation on Ser-3 by Ghrelin-O-Acyltransferase (GOAT). We have previously shown that Goat−/− mice developed severe hypoglycemia under 60% calorie restriction. Liver autophagy has been reported to play a crucial role in maintaining blood glucose during fasting. The present work was carried out to explore whether autophagy plays a role in the onset of hypoglycemia in Goat−/− mice. We observed a deficiency in autophagy in livers of calorie-restricted Goat−/− mice by showing lower expression level of LC3-II, an autophagy marker. This was further demonstrated by showing 10-fold fewer autolysosomes in livers of calorie-restricted Goat−/− mice as compared to the control mice (20 electron microscopic images analyzed for each group). We then went on to show that the deficiency in autophagy in Goat−/− mice can be restored by infusion of growth hormone. It can also be restored by injections of lactate, a gluconeogenic precursor, or octanoate, a fatty acid that spares the usage of glucose. Protein expression of p- STAT 5, a downstream target of growth hormone action, was significantly lower in livers of calorie-restricted Goat−/− mice, and was restored by infusion of growth hormone and by injections of lactate or octanoate. Protein expression levels of LC3-II and p-STAT 5 showed a strong correlation (r2=0.87, p<10-6) through the time course of calorie-restriction. Considered together, these data suggest that the onset of autophagy during calorie restriction is strongly correlated with the ghrelin-growth hormone axis, and that autophagy plays an important role in maintaining blood glucose homeostasis during chronic starvation.

General Notes

The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.

Table of Contents


Related URI