title: Fatty acid synthase is required for mammary gland development and milk production during lactation.
abstract: The mammary gland is one of the few adult tissues that strongly induce de novo fatty acid synthesis upon physiological stimulation, suggesting that fatty acid is important for milk production during lactation. The committed enzyme to perform this function is fatty acid synthase (FASN). To determine whether de novo fatty acid synthesis is obligatory or dietary fat is sufficient for mammary gland development and function during lactation, Fasn was specifically knocked out in mouse mammary epithelial cells. We found that deletion of Fasn hindered the development and induced the premature involution of the lactating mammary gland and significantly decreased medium- and long-chain fatty acids and total fatty acid contents in the milk. Consequently, pups nursing from Fasn knockout mothers experienced growth retardation and preweanling death, which was rescued by cross-fostering pups to a lactating wild-type mother. These results demonstrate that FASN is essential for the development, functional competence, and maintenance of the lactating mammary gland.
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Janel
authors.initials: J
authors.lastname: Suburu
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Michael
authors.initials: M
authors.lastname: Samuel
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thomas
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; and.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Kock
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Steven
authors.initials: S
authors.lastname: Kridel
authors.affiliation: The Synergistic Innovation Center for Food Safety and Nutrition, State Key Laboratory of Food Science and Technology, and School of Food Science and Technology, Jiangnan University, Wuxi, China; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina; yqchen@wakehealth.edu.
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000502:physiology*; D005260:Female; D007774:Lactation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism*
chemical_list: D054890:Fatty Acid Synthase, Type I
keywords: fatty acid synthase; gene knockout; lactation; lipid synthesis; mammary gland