Mechanisms for conjugated linoleic acid-mediated reduction in fat deposition

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-γ (PPARγ), a key transcription factor in adipocyte differentiation, requires an activating ligand; CLA are ligands for PPARγ. The concentration of PPARγ mRNA increases during adipocyte differentiation. In CLA-treated differentiating preadipocytes in culture, the PPARγ 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 PPARγ 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.

Implications

Conjugated linoleic acid (CLA) decreases fat deposition when fed to several mammalian species and chickens. The practicality of feeding CLA to a meat-producing animal, such as the pig, is yet to be determined because there are both positive and negative data. Among the mechanisms proposed to explain the CLA-mediated decreased fat deposition are increased energy expenditure, fat oxidation, fat cell lipid degradation, or fat cell destruction. Also, decreased fat cell precursors, fat cell development, fat synthesis, or desaturation of fats could decrease fat deposition. Some mechanisms appear to be species-specific. Other mechanisms may be secondary rather than the primary cause. The primary mechanism probably resides in regulation of a few key genes that control a number of aspects of metabolism. The transcription factor, PPARγ, is a candidate gene because it binds and is activated by CLA. However, the mechanism by which CLA reduces fat deposition remains unclear.

Key Words: Adipocytes, Dienoic Fatty Acids, Differentiation, Energy Metabolism, Lipid Metabolism, Tissue Proliferation

Ö2002 American Society of Animal Science. All rights reserved.
J. Anim. Sci. 80(E. Suppl. 2):E126-E134