This chapter discusses the preparation and effects of 5-(tetradecyloxy)-2-furoic acid (TOFA). TOFA reduces plasma triglyceride levels of both rats and monkeys, inhibits hepatic fatty acid synthesis both in vivo and in vitro, inhibits lipogenesis by isolated acini of lactating mammary gland, and inhibits cholesterolgenesis by isolated hepatocytes. The compound stimulates hepatic fatty acid oxidation and ketone body formation in vitro and inhibits glucose utilization by isolated hepatocytes and isolated acini. It is possible to prepare 10 mM solutions of TOFA in 20 mM NaOH, but the solution must be maintained at a high temperature. Aliquots of this solution can then be added to solutions containing albumin without the precipitation of TOFA. The effects of 50 μM TOFA on some of the metabolic processes of isolated hepatocytes are shown. Utilization of glucose carbon obtained by glycogenolysis is inhibited by TOFA, as is de novo fatty acid synthesis. TOFyl-CoA formation within intact hepatocytes can also be demonstrated. The inhibition of acetyl-CoA carboxylase by TOFyI-CoA is also elaborated.
ASJC Scopus subject areas
- Molecular Biology