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Title: Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice

Author
item KADEGOWDA, ANIL - UNIVERSITY OF MARYLAND
item Connor, Erin
item TETER, BEVERLY - UNIVERSITY OF MARYLAND
item SAMPUGNA, JOSEPH - UNIVERSITY OF MARYLAND
item DELMONTE, PIERLUIGI - FDA
item PIPEROVA, LILIANA - UNIVERSITY OF MARYLAND
item ERDMAN, RICHARD - UNIVERSITY OF MARYLAND

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/19/2010
Publication Date: 3/10/2010
Citation: Kadegowda, A.K., Connor, E.E., Teter, B.B., Sampugna, J., Delmonte, P., Piperova, L.S., Erdman, R.A. 2010. Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice. Journal of Nutrition. 140:919-924.

Interpretive Summary: Feeding of specific fatty acids to dairy cattle can alter the amount of fat produced in the milk. The mechanisms controlling these changes in milk fat production are not well understood. The present study was conducted using a lactating mouse model where mice were fed various individual fatty acids in the diet to assess the effects of the fatty acids on expression of genes in the liver and mammary gland of the mouse. Genes known to function in the regulation of fat synthesis were examined by a technique called quantitative real-time polymerase chain reaction. The results indicated feeding of a specific fatty acid called trans-7, cis-9-conjugated linoleic acid may be an important regulator of milk fat production. In addition, multiple genes (SREBP-1C, ChREBP, PPARG and INSIG1) that control the expression of other fat synthesis regulatory genes were implicated in the control of milk fat production. Finally, the effects of these fatty acids in the diet appeared to have greater effects on regulation of genes in the mammary gland than in the liver, suggesting the effects are locally controlled within the animal, rather than systemically regulated. Results of this work provide insight into how depression of milk fat synthesis occurs at the cellular level in response to feeding of specific fatty acids in dairy cattle, and may be useful for manipulating fat composition of milk.

Technical Abstract: The objectives were to examine the effects of several individual trans-18:1 isomers and t10c12-CLA on fat synthesis, and expression of lipogenic genes and transcription factors in liver and mammary tissues in lactating mice. Thirty lactating C57Bl6J mice were randomly assigned to 6 diets supplemented with one of the following isomers t7-, t9-, t11-18:1, t10c12-CLA or PHVO (partially hydrogenated vegetable oil) from day 6 to day 10 postpartum. Milk fat percentage was decreased by t10c12-CLA (44%; P<0.001), t7-18:1 (27%; P< 0.001) and PHVO (23%; P<0.001), compared to Control. Amounts of total CLA were greatest in milk of mice fed t7-18:1 (2.4%, P <0.01), followed by t10c12-CLA (1.9%, P <0.01) and t11-18:1 (1.1%, P <0.01). The increased CLA found in milk of mice fed t7-18:1 was a result of substantial endogenous synthesis of t7c9-CLA, representing 87 % of total CLA. In the mammary gland, t10c12-CLA decreased gene expression related to de novo FA synthesis (FASN, P<0.01; ACACA P<0.01), triacylglycerol formation (AGPAT, P<0.01), desaturation (SCD1, P<0.05; SCD2 P<0.05), transcriptional regulation (SREBP-1c, P<0.01; ChREBP, P<0.01); THRSP, P<0.01; PPARA P<0.05; PPARG, P<0.05). PHVO and t7-18:1 decreased the expression of AGPAT, SCD1 and THRSP (P<0.05). Mammary gene expression was not altered by t-9- or t-11-18:1. In liver, expression of AGPAT was significantly decreased by diets supplemented with t10c12-CLA (P<0.01), PHVO (P<0.01) and t7-18:1. Opposite to mammary gland, CLA up regulated hepatic PPARA (P<0.05) and decreased PPARG (P<0.05). There was a substantial increase in total FAME (per g of dry tissue) in liver of dams fed the t10c12-CLA- (81%, P<0.01), PHVO- (35%, P<0.05), t7-18:1- (38%, P<0.05), and t11-18:1- (26%, P<0.05) supplemented diets. The results demonstrated extensive conversion of t7-18:1 to t7c9-CLA in mammary and liver tissues of mice fed the t7-18:1 diet. The observed milk fat depression suggests potential involvement of t7c9-CLA in regulation of milk fat synthesis. In addition to SREBP-1C, the study establishes a role of ChREBP, PPARG and INSIG1 in regulation of milk fat synthesis. The effects of FA on lipogenic gene expression were more pronounced in mammary tissue than in liver.