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USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030-2600
1 Correspondence: 1100 Bates Street (phone: 713/798-7128; fax: 713/798-7130; E-mail: mersmann{at}bcm.tmc.edu).
Abstract
Potential mechanisms for the decreased fat deposition observed after oral administration of conjugated linoleic acids (CLA) to mice, rats, hamsters, humans, and pigs will be reviewed. Most mechanisms are based on experiments with rodents or rodent-derived cells. Administration of CLA results in an increased metabolic rate in intact mice, but not in rats or sows. There is a decreased respiratory quotient in mice and rats, suggesting increased fat oxidation. Bovine milk-fat synthesis is decreased. Rat adipocyte size is smaller, but cell number is unchanged. In mice, there is increased adipocyte apoptosis. In 3T3-L1 preadipocytes, a clonal cell line derived from rodents, CLA decreases proliferation. Human, but not porcine, preadipocyte proliferation was inhibited by CLA. Differentiation of 3T3-L1 preadipocytes was diminished by CLA in two laboratories, but increased in a third laboratory. In porcine and human preadipocytes, CLA acutely increased lipid deposition, but lipid content quickly reached a plateau. Peroxisome proliferator-activated receptor-
(PPAR), a key transcription factor in adipocyte differentiation, requires an activating ligand; CLA are ligands for PPAR. The concentration of PPAR mRNA increases during adipocyte differentiation. In CLA-treated differentiating preadipocytes in culture, the PPAR mRNA concentration was decreased, increased, or not significantly changed, providing little evidence for modulation of differentiation through this mechanism. However, CLA might act as an agonistic or antagonistic ligand for PPAR to control differentiation. The primary CLA isomer in ruminant tissues is cis 9, trans 11-CLA. Most synthetic CLA preparations contain a considerable amount of trans 10, cis 12-CLA, in addition to 9,11-CLA. The 10,12-CLA is responsible for the body composition changes in mice and for the decreased bovine milk-fat synthesis. The two CLA isomers equally reduced lipid deposition in porcine preadipocytes, whereas there is evidence for both a preferential effect of 10,12-CLA and no isomer distinction in human preadipocytes. Elucidation of the mechanism(s) for a CLA-mediated reduction in fat deposition remains elusive and may be species-specific.
2 This presentation would not be possible without the generous contribution of unpublished data by the following investigators: Mike Azain, Dale Bauman, Frank Dunshea, Ching-Yuan Hu, Michael McIntosh, Scott Mills, Jess Miner, Jack Odle, Michael Pariza, Fred Parrish, and Steve Smith. I thank each of you. I also thank Leslie Loddeke for editorial assistance. This review does not pretend to be comprehensive, but presents the author's interpretation of the current literature, including numerous unpublished observations. The review was completed in July, 2001. The reader should consult the literature of 2001 and 2002 to learn of updates in this rapidly expanding field.
3 This work is a publication of the USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas. This project has been funded in part with federal funds from the USDA/ARS under Cooperative Agreement No. 58-6250-6001. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement from the U.S. government.
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