PMID- 21281598 OWN - NLM STAT- MEDLINE DCOM- 20110511 LR - 20211203 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 508 IP - 1 DP - 2011 Apr 1 TI - 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. PG - 87-92 LID - 10.1016/j.abb.2011.01.015 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Moriya, Hitomi AU - Moriya H AD - Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. FAU - Uchida, Kana AU - Uchida K FAU - Okajima, Tetsuya AU - Okajima T FAU - Matsuda, Tsukasa AU - Matsuda T FAU - Nadano, Daita AU - Nadano D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110131 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Enzymes) RN - 0 (Fatty Acids) RN - 0 (Glycolipids) RN - 0 (Glycoproteins) RN - 0 (Protein Kinase Inhibitors) RN - 0 (milk fat globule) RN - EC 2.3.1.85 (Fatty Acid Synthases) RN - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 6.4.1.2 (Acetyl-CoA Carboxylase) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - ATP Citrate (pro-S)-Lyase/metabolism MH - Acetyl-CoA Carboxylase/metabolism MH - Animals MH - Enzymes/*metabolism MH - Fatty Acid Synthases/metabolism MH - Fatty Acids/*biosynthesis MH - Female MH - Glycolipids/*metabolism MH - Glycoproteins/*metabolism MH - Lipid Droplets MH - Mice MH - Mice, Inbred BALB C MH - Milk/*enzymology MH - Protein Kinase Inhibitors/pharmacology MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases/antagonists & inhibitors MH - Time Factors EDAT- 2011/02/02 06:00 MHDA- 2011/05/12 06:00 CRDT- 2011/02/02 06:00 PHST- 2010/10/26 00:00 [received] PHST- 2011/01/21 00:00 [revised] PHST- 2011/01/24 00:00 [accepted] PHST- 2011/02/02 06:00 [entrez] PHST- 2011/02/02 06:00 [pubmed] PHST- 2011/05/12 06:00 [medline] AID - S0003-9861(11)00039-7 [pii] AID - 10.1016/j.abb.2011.01.015 [doi] PST - ppublish SO - Arch Biochem Biophys. 2011 Apr 1;508(1):87-92. doi: 10.1016/j.abb.2011.01.015. Epub 2011 Jan 31.