The objectives of the dissertation research were to determine the role of denovo synthesized fatty acids (DNFA) in the regulation of milk fat synthesis. Milk fat responses to increasing amounts of short- and medium-chain fatty acids (SMCFA), added in the proportion as synthesized denovo, were studied in lactating dairy cows. The results showed a significant linear increase in milk fat concentration with SMCFA supplementation. However, milk fat yield was similar for all treatments.

A subsequent study was aimed at increasing the availability of SMCFA during trans-10, cis-12 CLA-induced milk fat depression (MFD) in lactating dairy cows to determine whether SMCFA can rescue part of CLA-induced MFD. Post-ruminal infusion of butterfat (BF) was used as a source of SMCFA. The BF treatment was compared to a mixture of fats containing only the long-chain FA (LCFA) with or without trans-10, cis-12 CLA infusion. Milk fat content and yield were significantly reduced with trans-10, cis-12 CLA. However, increased availability of SMCFA with BF infusion had no effects on milk fat yield and concentration. Trans-10, cis-12 CLA significantly reduced the mRNA expression of transcription factor SREBP-1c along with its downstream targets including ACC,FASN, LPL, SCD and AGPAT. The increased availability of SMCFA had no effect on either lipogenic gene or protein expression suggesting that nutritional manipulation was not sufficient to rescue trans-10, cis-12 CLA-induced MFD.

Finally, the effects of combination of a Rosiglitazone (ROSI), a PPAR-γ agonist, and trans-10, cis-12 CLA were examined on mammary and hepatic lipogenesis in lactating mice. Mammary lipogenesis was significantly reduced with trans-10, cis-12 CLA, reducing the milk fat content and mRNA expression of lipogenic transcription factors SREBP1-c and PPAR- γ. Trans-10, cis-12 CLA significantly increased hepatic lipid accumulation, while the mRNA expression of SREBP1-c and PPAR- γ were not altered. On the contrary, ROSI had no effects on mammary lipogenesis. However, ROSI significantly rescued trans-10, cis-12 CLA-induced hepatic steatosis.