Growth hormone acts on liver to stimulate autophagy, support glucose production, and preserve blood glucose in chronically starved mice

When mice are subjected to 60% calorie restriction for several days, they lose nearly all of their body fat. Although the animals lack energy stores, their livers produce enough glucose to maintain blood glucose at viable levels even after a 23-hour fast. This adaptation is mediated by a marked increase in plasma growth hormone (GH), which is elicited by an increase in plasma ghrelin, a GH secretagogue. In the absence of ghrelin, calorie-restricted mice develop hypoglycemia, owing to diminished glucose production. To determine the site of GH action, in the current study we used CRISPR/Cas9 and Cre recombinase technology to produce mice that lack GH receptors selectively in liver (L-Ghr−/− mice) or in adipose tissue (Fat-Ghr−/− mice). When subjected to calorie restriction and then fasted for 23 hours, the L-Ghr−/− mice, but not the Fat-Ghr−/− mice, developed hypoglycemia. The fall in blood glucose in L-Ghr−/− mice was correlated with a profound drop in hepatic triglycerides. Hypoglycemia was prevented by injection of lactate or octanoate, two sources of energy to support gluconeogenesis. Electron microscopy revealed extensive autophagy in livers of calorie-restricted control mice but not in L-Ghr−/− mice. We conclude that GH acts through its receptor in the liver to activate autophagy, preserve triglycerides, enhance gluconeogenesis, and prevent hypoglycemia in calorie-restricted mice, a model of famine.

Effects of Composite Supplement Containing Collagen Peptide and Ornithine on Skin Conditions and Plasma IGF-1 Levels—A Randomized, Double-Blind, Placebo-Controlled Trial

Aging-associated changes of skin conditions are a major concern for maintaining quality of life. Therefore, the improvement of skin conditions by dietary supplementation is a topic of public interest. In this study, we hypothesized that a composite supplement containing fish derived-collagen peptide and ornithine (CPO) could improve skin conditions by increasing plasma growth hormone and/or insulin-like growth factor-1 (IGF-1) levels. Twenty-two healthy Japanese participants were enrolled in an 8-week double-blind placebo-controlled pilot study. They were assigned to either a CPO group, who were supplemented with a drink containing CPO, or an identical placebo group. We examined skin conditions including elasticity and transepidermal water loss (TEWL), as well as plasma growth hormone and IGF-1 levels. Skin elasticity and TEWL were significantly improved in the CPO group compared with the placebo group. Furthermore, only the CPO group showed increased plasma IGF-1 levels after 8 weeks of supplementation compared with the baseline. Our results might suggest the novel possibility for the use of CPO to improve skin conditions by increasing plasma IGF-1 levels.