TY - JOUR
T1 - Biochemical studies on the mechanism of action of liver poisons II. Induction of fatty livers
AU - Glaser, G.
AU - Mager, J.
PY - 1972/2/29
Y1 - 1972/2/29
N2 - Administration of adenine or its nucleotide derivatives (3′(2′)-AMP, 5′-AMP and ATP) to rats prevented the induction of fatty livers by ethionine, carbon tetrachloride and Pactamycin, but failed to relieve the inhibition of protein synthesis in vivo and the derangement of the triglyceride transport from the liver caused by these hepatotoxins. The antidotal effect of the exogenous ATP precursors against the steatogenic action of the liver poisons appeared to be unrelated to the reversal of the ATP depletion observed in ethionine poisoning, since no appreciable changes in the hepatic ATP content occurred in rats treated with carbon tetrachloride or Pactamycin under the conditions employed in this study. Adenine and its congeners induced a marked depression of the plasma free fatty acid level and a concomitant elevation of the blood glucose concentration. Adrenalectomy abolished the hyperglycemic effect of adenine nucleotides but allowed their depressive influence on the plasma free fatty acids to persist, indicating that the latter phenomenon was not entirely attributable to the well-known inhibitory effect of glucose on free fatty acid mobilization. It was concluded that adenine and the congerous nucleotides exerted their protective action against fatty liver induction by curtailing the influx of free fatty acids into the liver and thereby limiting the extent of triglyceride synthesis. This interpretation is also supported by the correlation between the female-sex dependency of the ethionine-induced hypoglycemia and increased fatty acid mobilization on the one hand, and the greater susceptibility of the female rat to the steatogenic action of this poison on the other.
AB - Administration of adenine or its nucleotide derivatives (3′(2′)-AMP, 5′-AMP and ATP) to rats prevented the induction of fatty livers by ethionine, carbon tetrachloride and Pactamycin, but failed to relieve the inhibition of protein synthesis in vivo and the derangement of the triglyceride transport from the liver caused by these hepatotoxins. The antidotal effect of the exogenous ATP precursors against the steatogenic action of the liver poisons appeared to be unrelated to the reversal of the ATP depletion observed in ethionine poisoning, since no appreciable changes in the hepatic ATP content occurred in rats treated with carbon tetrachloride or Pactamycin under the conditions employed in this study. Adenine and its congeners induced a marked depression of the plasma free fatty acid level and a concomitant elevation of the blood glucose concentration. Adrenalectomy abolished the hyperglycemic effect of adenine nucleotides but allowed their depressive influence on the plasma free fatty acids to persist, indicating that the latter phenomenon was not entirely attributable to the well-known inhibitory effect of glucose on free fatty acid mobilization. It was concluded that adenine and the congerous nucleotides exerted their protective action against fatty liver induction by curtailing the influx of free fatty acids into the liver and thereby limiting the extent of triglyceride synthesis. This interpretation is also supported by the correlation between the female-sex dependency of the ethionine-induced hypoglycemia and increased fatty acid mobilization on the one hand, and the greater susceptibility of the female rat to the steatogenic action of this poison on the other.
UR - http://www.scopus.com/inward/record.url?scp=0015008298&partnerID=8YFLogxK
U2 - 10.1016/0304-4165(72)90074-8
DO - 10.1016/0304-4165(72)90074-8
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C2 - 5144284
AN - SCOPUS:0015008298
SN - 0304-4165
VL - 261
SP - 500
EP - 507
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 2
ER -