Stable Isotopes and Mass Isotopomer Study of Fatty Acid and Cholesterol Synthesis

Abstract

Cholesterol and fatty acids are two major components of the lipid bilayer conferring physical and functional properties to the plasma membrane. A highly regulated de novo cholesterogenesis pathway is required for membranogenesis of the normal growth and maintenance of animal cells (1,2). Thus, rapidly growing tissues such as the brain of newborn rat pups have enhanced de novo cholesterogenesis in comparison to the adult brain (3). Conversely, slow turnover tissues such as the kidney have reduced cholesterogenesis (4). Numerous studies have shown that this regulation of lipogenesis is abnormal or absent when cells undergo malignant transformation (5, 6), and increased de novo lipogenesis has been found to strongly associate with the incidence of a number of cancers. In addition, dietary or hormonal factors which affect the regulation of lipogenesis may potentially alter the risk of development of certain cancers as suggested by the association between dietary fat intake and breast cancer risk in many epidemiological studies. The mechanism by which dietary and hormonal factors increase the risk of development of certain cancers is not known. Whether modification of dietary fat intake has any effect on the turnover of cholesterol and fatty acids or influence on the risk of developing cancer remains to be studied with the appropriate techniques.

Supported in part by PHS grants R01-DK46353. The GC/MS Facility is supported by PHS grants M01-RR00425 to the General Clinical Research Center, and P01-CA42710 to the UCLA Clinical Nutrition Research Unit, Stable Isotope Core.