Radioiodinated BMIPP as a potential probe for hepatic fatty acid metabolism: Evaluation in mice at different feeding status

Objectives Alteration of fatty acids (FA) metabolism in the liver leads to various diseases including hepatic steatosis. Therefore, understanding of hepatic FA metabolism is useful for evaluation of the diseases. A FA analog, ¹²³I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (¹²³I-BMIPP) is widely used for the diagnosis of cardiac FA metabolism, however the intrahepatic kinetics has not been investigated in detail. Thus, in order to clarify potentials of ¹²³I-BMIPP for imaging hepatic FA metabolism, we determined hepatic distribution/metabolism of ¹²⁵I-BMIPP in mice at various metabolic status induced by fasting.

Methods Fed or fasted (6, 12, and 24 h fasting) mice were injected with ¹²⁵I-BMIPP. Radioactivity in the liver was measured at 1, 5, 10, 30, 60 and 120 min after the injection (n=5 in each time point). Lipid fraction was extracted from the liver by the Folch method, and radioactivity in the lipid fraction (e.g. unchanged ¹²⁵I-BMIPP and triglyceride (TG)) was analyzed by thin-layer chromatography.

Results The hepatic radioactivity in the fasted groups was higher than in the fed group, and this tendency was depending on the fasting time (AUC: 35, 45, 56, 59 (%ID/g/kg)×min for fed, 6, 12, 24 h-fasting). Radioactivity in the TG fraction was also higher in the fasted groups than the fed group (AUC: 6, 12, 31, 37 (%ID/g/kg)×min for fed, 6, 12, 24 h-fasting). It is known that FA released from adipose tissues can be re-esterified to produce TG in the liver under fasting when influx of FA exceeds hepatic oxidation capacity, which may explain the present results.

Conclusions Hepatic distribution of ¹²⁵I-BMIPP was increased by fasting and further elevation was seen by extension of fasting time. Increased storage as TG by fasting may be the reason for the difference. ¹²⁵I-BMIPP can detect changes in hepatic FA metabolism induced by fasting, indicating potentials ¹²³I-BMIPP for imaging hepatic FA metabolism.