biostudies-literatureZhang YHHS | National Institutes of HealthNHLBI NIH HHSNIGMS NIH HHS1226-31https://www.ebi.ac.uk/biostudies/studies/S-EPMC4313810biostudies-literatureUnknown112(4)Plasma growth hormone (GH) and hepatic autophagy each have been reported to protect against hypoglycemia in the fasted state, but previous data have not linked the two. Here we demonstrate a connection using a mouse model of fasting in a fat-depleted state. Mice were subjected to 1 wk of 60% calorie restriction, causing them to lose nearly all body fat. They were then fasted for 23 h. During fasting, WT mice developed massive increases in plasma GH and a concomitant increase in hepatic autophagy, allowing them to maintain viable levels of blood glucose. In contrast, lethal hypoglycemia occurred in mice deficient in the GH secretagogue ghrelin as a result of knockout of the gene encoding ghrelin O-acyltransferase (GOAT), which catalyzes a required acylation of the peptide. Fasting fat-depleProceedings of the National Academy of Sciences of the United States of AmericaReduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: reversal by growth hormone.PMC4313810HL20948T32 GM008014P01 HL020948ST32GM08014Zhang YFang FZhao TJGoldstein JLBrown MSfalseReduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: reversal by growth hormone.Plasma growth hormone (GH) and hepatic autophagy each have been reported to protect against hypoglycemia in the fasted state, but previous data have not linked the two. Here we demonstrate a connection using a mouse model of fasting in a fat-depleted state. Mice were subjected to 1 wk of 60% calorie restriction, causing them to lose nearly all body fat. They were then fasted for 23 h. During fasting, WT mice developed massive increases in plasma GH and a concomitant increase in hepatic autophagy, allowing them to maintain viable levels of blood glucose. In contrast, lethal hypoglycemia occurred in mice deficient in the GH secretagogue ghrelin as a result of knockout of the gene encoding ghrelin O-acyltransferase (GOAT), which catalyzes a required acylation of the peptide. Fasting fat-deple2015-01-01T00:00:00Z2015 Jan2025-04-21T19:48:33.71Z2019-03-27T01:44:25ZS-EPMC43138102558351310.1073/pnas.1423643112