The fate and intermediary metabolism of stearic acid

Coming from the Greek for hard fat, stearic acid represents one of the most abundant FA in the Western diet. Otherwise known as n-octadecanoic acid (18:0), stearate is either obtained in the diet or synthesized by the elongation of palmitate, the principal product of the FA synthase system in animal cells. Stearic acid has been shown to be a very poor substrate for TG synthesis, even as compared with other saturated fats such as myristate and palmitate, and in human studies stearic acid has been shown to generate a lower lipemic response than medium-chain saturated FA. Although it has been proposed that this may be due to less efficient absorption of stearic acid in the gut, such findings have not been consistent. Along with palmitate, stearate is the major substrate for the enzyme stearoyl-CoA desaturase, which catalyzes the conversion of stearate to oleate, the preferred substrate for the synthesis of TG and other complex lipids. In mice, targeted disruption of the stearoyl-CoA desaturase-1 (SCD1) gene results in the generation of a lean mouse that is resistant to diet-induced obesity and insulin resistance. SCD1 also has been shown to be a key target of the anorexigenic hormone leptin, thus underscoring the importance of this enzyme, and consequently the cellular stearate-to-oleate ratio, in lipid metabolism and potentially in the treatment of obesity and related disorders.