A high rate of lipogenesis in obese mice plays a major role in their excessive deposition of body
lipid. Inhibition of lipogenesis may decrease their
obesity. Therefore, we have investigated the effects of
sodium 2-n-pentadecyl-benzimidazole-5-carboxylate (
M & B 35347B), an inhibitor of
acetyl-CoA carboxylase, on in-vivo lipogenesis in obese and lean mice. It significantly inhibited hepatic
cholesterol and
fatty acid synthesis, measured using 3H2O, in both lean and obese mice, with or without a
glucose load. Brown adipose tissue (scapular) lipogenesis was decreased by
M & B 35347B in obese mice but not in lean mice. In white adipose tissue,
M & B 35347B did not affect the rates of lipogenesis in either scapular white, inguinal or epididymal depots of obese mice, or the inguinal and scapular white depot of lean mice. However, it doubled lipogenesis in the epididymal fat pad of lean mice. After a
glucose load, lipogenesis in the lean epididymal fat pad was not inhibited but that in the inguinal depot was.
M & B 35347B inhibited
acetyl CoA carboxylase of adipose tissue in vitro but only a small inhibition was detected after in-vivo treatment. These different responses according to type of mouse, treatment and tissue site appear to stem from differences in inhibitor concentration and the importance of
acetyl CoA carboxylase as the rate-limiting
enzyme of lipogenesis. The
weight gain of obese mice dosed orally (200 mg
M & B 35347B/kg daily) for 60 days was unaffected and they continued to deposit excess body fat. This presumably occurred because of the lack of inhibition of
fatty acid synthesis in white adipose tissue.