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* Department of Animal Sciences, Oregon State University, Corvallis OR 97331 and
Hill's Pet Nutrition, Inc., Topeka, KS 66601
Conjugated linoleic acid (CLA; 18:2) is a group of isomers (mainly
9-cis, 11-trans and 10-trans,
12-cis) of linoleic acid. CLA is the product of rumen
fermentation and can be found in the milk and muscle of ruminants.
Animals fed CLA have a lower body fat content. The objective of this
study was to establish the possible mechanisms by which CLA affects
adipogenesis. 3T3-L1 is a well-established cell line that is used
extensively in studying adipocyte biology. These cells typically grow
in a culture medium until they reach confluence, at which time they are
induced to differentiate by hormonal treatment (d 0). Treatment of
3T3-L1 cells with 25 to 100 µmol/L CLA inhibited differentiation in a
dose-dependent manner, while linoleic acid treatment did not differ
from DMSO-treated controls. Continuous treatment from d -2, -1, 0 or
2 to d 8 and treatment from d -2 to d 0 and from d 0 to d 2 inhibited
differentiation. Differentiation was monitored morphologically (oil
Red-O staining), enzymatically (reduction of activity of
glycerol-3-phosphate dehydrogenase), and by northern analysis of
peroxisome proliferator-activated receptor
2, CCAAT/enhancer binding
protein
and adipocyte specific protein 2 mRNA. CLA inhibited cell
proliferation of nonconfluent cells but did not affect cell division of
confluent cells, as indicated by 5-bromo-2'-deoxyuridine incorporation
and mitochondria metabolism. Therefore, CLA inhibited differentiation
before confluence and during induction. However, cellular proliferation
was only inhibited prior to induction. These results imply that fat
reduction caused by CLA treatment may be attributed to its inhibition
of both proliferation and differentiation of preadipocytes in
animals.
KEY WORDS: adipocytes conjugated linoleic acid differentiation proliferation fatty acids
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