title: Trans-10, cis-12 CLA dose-dependently inhibits milk fat synthesis without disruption of lactation in C57BL/6J mice.
abstract: BACKGROUND
  Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a potent inhibitor of milk fat synthesis in mammals. In the cow, 10 g/d of 10,12 CLA specifically and reversibly inhibits mammary lipogenesis, whereas substantially higher doses are not specific and cause a generalized inhibition of milk synthesis.
  
  
  OBJECTIVE
  The objective of this study was to validate a lactating mouse model by establishing the dose response, specificity, and reversibility of the inhibition of milk fat synthesis by 10,12 CLA.
  
  
  METHODS
  Lactating mice (C57BL/6J) received daily doses of 0 (control), 7, 20, or 60 mg of 10,12 CLA for 5 d during established lactation. A second group of lactating mice was treated with 20 mg/d of 10,12 CLA for 4 d and followed post-treatment to evaluate reversibility.
  
  
  RESULTS
  CLA decreased pup growth with a 49% decrease occurring with 60 mg/d of CLA. Milk fat percentage was decreased 11% and 20% with the 7 and 20 mg/d dose, respectively, and all CLA treatments had a decreased concentration of de novo synthesized fatty acids (FAs) in milk fat. In agreement, 20 mg/d of 10,12 CLA decreased the lipogenic capacity of mammary tissue by 30% and mammary expression of FA synthase (Fasn), sterol response element binding protein 1 (Srebf1), and thyroid hormone responsive spot 14 (Thrsp) by 30-60%, whereas milk protein percentage and mammary expression of α-lactalbumin (Lalba) were unaltered. This dose of CLA reduced pup growth by nearly 20% and milk de novo synthesized FAs by >35%, and these effects were completely reversed 5 d after 10,12 CLA treatment was terminated.
  
  
  CONCLUSIONS
  Inhibition of mammary lipogenesis by 10,12 CLA is dose-dependent in the mouse, with a specific and reversible reduction in milk fat synthesis at the 20 mg/d dose and additional nonspecific effects on milk synthesis at higher CLA doses.
authors.affiliation: Department of Animal Science, Penn State University, University Park, PA; and.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harvatine
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Robblee
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thorn
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Yves R
authors.initials: YR
authors.lastname: Boisclair
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY deb6@cornell.edu.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bauman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D007768:Lactalbumin / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000187:drug effects*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry*; D008894:Milk Proteins / Q000378:metabolism; D023421:Models, Animal; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D008894:Milk Proteins; D009687:Nuclear Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C501477:Thrsp protein, mouse; D014157:Transcription Factors; D007768:Lactalbumin; D064429:Fatty Acid Synthases
keywords: Srebf1; Thrsp; conjugated linoleic acid; mammary lipogenesis; milk fat synthesis