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Significance Famine kills millions of people each year. Survival requires the maintenance of blood glucose. Famine depletes body fat, thereby removing a source of energy for hepatic glucose production. Here we used a mouse model of fat depletion to show that growth hormone (GH) maintains blood sugar by stimulating hepatic autophagy, the process by which the liver digests its organelles to provide energy and substrates for producing glucose. When fat-depleted mice are fasted, their stomachs secrete ghrelin, a GH secretagogue. The resultant elevation in GH stimulates hepatic autophagy. In mice lacking ghrelin, GH fails to rise appropriately, hepatic autophagy is reduced, and mice die from hypoglycemia. These studies demonstrate a ghrelin-GH-autophagy axis that is required for survival in famine.

Reduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: Reversal by growth hormone