Regulation of fat synthesis by conjugated linoleic acid: Lactation and the ruminant model

Conjugated linoleic acid (CLA) isomers effect an impressive range of biological processes including the ability to inhibit milk fatty acid synthesis. Although this has been demonstrated in several mammals, research has been most extensive with dairy cows. The first isomer shown to affect milk fat synthesis during lactation was trans-10, cis-12 CLA, and its effects have been well characterized including dose-response relationships. Recent studies have tentatively identified 2 additional CLA isomers that regulate milk fat synthesis. Regulation by CLA occurs naturally in dairy cows when specific CLA isomers produced as intermediates in rumen biohydrogenation act to inhibit milk fat synthesis; this physiological example of nutritional genomics is referred to as diet-induced milk fat depression. Molecular mechanisms for the reduction in mammary lipid synthesis involve a coordinated down-regulation of mRNA expression for key lipogenic enzymes associated with the complementary pathways of milk fat synthesis. Results provide strong evidence of a role for sterol response element-binding protein 1 and Spot 14 in this translational regulation. Effects of CLA on body fat accretion have also been investigated in nonlactating animals, but CLA effects on mammary fatty acid synthesis occur at an order-of-magnitude lower dose and appear to involve very different mechanisms than those proposed for the antiobesity effects of CLA. Overall, results demonstrate the unique value of cows as a model to investigate the role of CLA in the regulation of milk fat synthesis during lactation.