title: Secretion of three enzymes for fatty acid synthesis into mouse milk in association with fat globules, and rapid decrease of the secreted enzymes by treatment with rapamycin.
abstract: The mammary epithelium produces numerous lipid droplets during lactation and secretes them in plasma membrane-enclosed vesicles known as milk fat globules. The biogenesis of such fat globules is considered to provide a model for clarifying the mechanisms of lipogenesis in mammals. In the present study, we identified acetyl coenzyme A carboxylase, ATP citrate lyase, and fatty acid synthase in mouse milk. Fractionation of milk showed that these three enzymes were located predominantly in milk fat globules. The three enzymes were resistant to trypsin digestion without Triton X-100, indicating that they were not located on the outer surface of the globules and thus associated with the precursors of the globules before secretion. When a low dose of rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), was injected into lactating mice, the levels of the three enzymes in milk were decreased within 3h after injection. Since the protein levels of the three enzymes in tissues were not obviously altered by this short-term treatment, known transcriptional control by mTOR signaling was unlikely to account for this decrease in their levels in milk. Our findings suggest a new, putatively mTOR-dependent localization of the three enzymes for de novo lipogenesis.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Moriya
authors.forename: Kana
authors.initials: K
authors.lastname: Uchida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okajima
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsuda
authors.forename: Daita
authors.initials: D
authors.lastname: Nadano
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D004798:Enzymes / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D006017:Glycolipids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D066292:Lipid Droplets; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D004798:Enzymes; D005227:Fatty Acids; D006017:Glycolipids; D006023:Glycoproteins; D047428:Protein Kinase Inhibitors; C110367:milk fat globule; D064429:Fatty Acid Synthases; D001275:ATP Citrate (pro-S)-Lyase; D058570:TOR Serine-Threonine Kinases; D000103:Acetyl-CoA Carboxylase; D020123:Sirolimus