Author:
de Toro-Martín Juan,Fernández-Marcelo Tamara,González-Rodríguez Águeda,Escrivá Fernando,Valverde Ángela M.,Álvarez Carmen,Fernández-Millán Elisa
Abstract
AbstractMaternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.
Publisher
Springer Science and Business Media LLC
Reference53 articles.
1. Girard, J., Ferré, P., Pégorier, J. P. & Duée, P. H. Adaptations of glucose and fatty acid metabolism during perinatal period and suckling-weaning transition. Physiol. Rev. 72, 507–562 (1992).
2. Kondomerkos, D. J., Kalamidas, S. A., Kotoulas, O. B. & Hann, A. C. Glycogen autophagy in the liver and heart of newborn rats. The effects of glucagon, adrenalin or rapamycin. Histol. Histopathol. 20, 689–696 (2005).
3. Kalamidas, S. A. & Kotoulas, O. B. The degradation of glycogen in the lysosomes of newborn rat hepatocytes: glycogen-, maltose- and isomaltose-hydrolyzing acid alpha glucosidase activities in liver. Histol. Histopathol. 14, 23–30 (1999).
4. Zhao, H., Tang, M., Liu, M. & Chen, L. Glycophagy: An emerging target in pathology. Clin. Chim. Acta 484, 298–303 (2018).
5. Efeyan, A. et al. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 493, 679–683 (2013).
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