Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver

Galit Pinto, Biana Shtaif, Moshe Phillip, Galia Gat-Yablonski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Our previous data suggested that the histone deacetylase (HDAC) SIRT1 is involved in mediating the effect of nutrition on growth. The aim of the present research was to study the mechanism by which additional HDACs may be involved in nutrition-induced linear growth. The in vivo studies were performed in young male Sprague-Dawley rats that were either fed ad libitum (AL) or subjected to 10. days of 40% food restriction (RES) and then refed (CU). For in vitro studies, Huh7 hepatoma cells were used. Food restriction led to significant reduction in liver weight, concomitant with increased autophagy (i.e., a decrease in the level of P62 and an increase in the expression level of Ambra1 and Atg16L2 genes in the RES group). At the same time, we found that the level of HDAC10 was significantly increased. Overexpression of HDAC10 in Huh7 hepatoma cells led to reduced cell viability and increased autophagy as shown by increased conversion of LC3-I to LC3-II. An increase in the level of HDAC10 was also obtained when mTOR was inhibited by Rapamycin. siRNA directed against HDAC10 abolished the effect of Rapamycin on cell viability and Ambra1 and Atg16L2 increased expression. These results suggest that increased levels of HDAC10 may mediate the effect of malnutrition on growth attenuation and autophagy. Deciphering the role of epigenetic regulation in the nutrition-growth connection may pave the way for the development of new forms of treatment for children with growth disorders.

Original languageEnglish
Pages (from-to)171-180
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume27
DOIs
StatePublished - 1 Jan 2016

Funding

FundersFunder number
Galit Pinto for the Sackler Faculty of Medicine, Tel Aviv University
Bill and Melinda Gates Foundation

    Keywords

    • Autophagy
    • Catch-up growth
    • Food restriction
    • HDAC10
    • Liver

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