ESPE Abstracts (2016) 86 FC13.1

Quantitative Proteomic of Rat Livers Shows a Major Reprogramming of Mitochondrial Enzymes in Food-Restriction and Increased Stress Hallmarks in Ad Libitum Feeding

Galia Gat-Yablonskia,b, Andrija Finkac, Galit Pintob, Manfredo Quadronid, Biana Shtaifb & Pierre Goloubinoffd

aSchneider Children’s Medical Center, Petach-Tikva, Israel; bTel Aviv University, Tel Aviv, Israel; cUniversity of Zadar, Zadar, Croatia; dUniversity of Lausanna, Lausanna, Switzerland

Background: Studies in young mammals on the qualitative and quantitative molecular effects of food restriction (RES) and re-feeding, leading to catch up growth (CU) are scarce. Whereas RES may lead to growth and developmental deficits in children, it is a proven treatment to prolong life in all animals checked.

Objective and hypotheses: We used MS analysis to understand how RES might lead to growth attenuation and prolonged life span and identify the major qualitative and quantitative changes in liver proteins.

Method: We used quantitative MS proteomic analysis of whole rat livers.

Results: Over 1900 common proteins were significantly quantified in livers of ad libitum, RES- and re-fed rats, which summed up into 95% of the total protein mass of the cells. In RES livers, a strong increase of mitochondrial catabolic enzymes was observed, alongside a decrease of cytosolic molecular chaperones, which are hallmarks of cellular stress. Following a single day of ad libitum re-feeding, the significant differences of protein levels in RES were nearly fully reversed.

Conclusion: The quantitative and qualitative protein values suggested that RES is not a stressful condition, as it necessitated only minimal levels of HSP-chaperones to maintain an optimal quali'ty of protein folding, thereby providing most advantageous conditions for an extended life span. In contrast, the protein profile of the ad libitum regimen was that of a chronic stressful condition necessitating constant high levels of HSP-chaperones to maintain protein homeostasis. The data thus suggests that the Ad libitum regimen brings a continuous strain on the protein quality control machineries of the cell, which may decrease the time of onset of aging and shorten life span.

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