Exploring the mechanisms of in vivo regulation of liver protein breakdown in the rat by the use of the new antilipolytic-agent model.
In this study, we explored the changes in the rate of protein degradation in liver cells in vivo, using a method based on the physiological stimulation of liver autophagy. Male albino rats 1, 2, 6, 12 and 24 months old were fasted overnight, and then received an injection of the antilipolytic agent 3,5-dimethylpyrazole (DMP) to evoke a sudden shortage of lipid fuel. A comparison was made with the in vivo effects of glucagon by giving the 2-month-old group an intraperitoneal injection of this hormone. Samples of liver were taken after 0, 15, 20, 30, 60 and 150 min and processed for electron microscopy, and groups of rats were subjected to short-term single pass liver perfusion. Results show that in the younger age-groups, the DMP stimulation of liver autophagy and amino acid release is highly significant, and compares favourably with the glucagon model of induction of the autophagic process. With older rats, an age-related longer time-lag of the autophagic response and a decrease in the effect of DMP were observed. In conclusion, hormones may activate autophagy, whereas levels of plasma amino acids may tune down the process to adjust the availability of the substrate to tissue needs.
Del Roso
A
A
Centro Interdipartimentale di Ricerca sull'Invecchiamento, Università di Pisa, Italy.
Bombara
M
M
Fierabracci
V
V
Fosella
P V
PV
Gori
Z
Z
Masini
M
M
Masiello
P
P
Pollera
M
M
Bergamini
E
E
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000008:administration & dosage; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011720:Pyrazoles; D005934:Glucagon; C027635:3,5-dimethylpyrazole