Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #142675
Title: ISOMERS OF CONJUGATED LINOLEIC ACID MODULATE HUMAN PREADIPOCYTE DIFFERENTIATION

Author
item McNeel, Ronald
item Smith, O'Brian
item Mersmann, Harry

Submitted to: In Vitro Cellular and Developmental Biology - Animal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2003
Publication Date: 9/30/2003
Citation: McNeel, R.L., Smith, E.O., Mersmann, H.J. 2003. Isomers of conjugated linoleic acid modulate human preadipocyte differentiation. In Vitro Cellular and Developmental Biology - Animals. 39(8-9):375-382.

Interpretive Summary: An epidemic of obesity is overtaking both children and adults all over the world. This is a huge, expensive health problem, because obesity puts people at risk for high blood pressure, diabetes, heart disease, stroke, and different types of cancer. Unfortunately, many people in this fast-paced era cite time constraints in their preference for fast (high-fat) food outlets and avoidance of exercise. In light of these realities, a pragmatic search is on for the proverbial "magic bullet." If a safe weight-loss pill could be found, it would be a helpful addition to any attempt to diet or exercise. Supplement makers are promoting conjugated linoleic acid (CLA) pills to the public, claiming that CLA reduces fat mass. A certain type of CLA has been found to reduce fat in study animals, but the effects of CLA have only been marginal in humans, based on studies to date. That might be due to species differences or the CLA dose used. One way to alter fat deposition would be to modulate and try to stop preliminary fat cells from spreading in the body. Previous studies from three labs using a rat cell line have shown a CLA dose-dependent reduction in proliferation, but the effects reported on differentiation have been mixed. We tested the effects of two types of CLA on human pre-fat cells in our laboratory. We incubated such cells in separate media containing the two types of CLA, and set up controls for comparison, then watched what happened for 17 days. At the end, we saw that the cell number had multiplied in all groups, but compared to the controls, both types of CLA reduced the cell number by 30 to 35 percent. CLA of both types significantly reduced proliferation. It was particularly interesting that at the dose levels we used, both types of CLA increased differentiation, although to a different extent over different periods of time. Based on these early results, it seems possible that some formulation of CLA in greater doses might ultimately help reduce fat in humans. However, that is left to speculation until more studies are done in human cells and in humans themselves.

Technical Abstract: Conjugated linoleic acids (CLAs) reduce fat deposition in several mammalian species. Among the proposed mechanisms for this effect are reduced preadipocyte proliferation and differentiation. We measured proliferation and differentiation of cultured human preadipocytes treated with CLAs. Preadipocytes were differentiated with insulin, hydrocortisone, transferrin, and 10% fetal bovine serum, with isobutyl-methylxanthine included for the first 2 d. The differentiation medium contained 200 microM oleic acid (C18:1), 50 microM cis-9,trans-11-CLA (9,11-CLA), or 50 microM trans-10,cis-12-CLA (10,12-CLA); the negative control medium contained no added fatty acid, and the cells did not differentiate. Cell number increased three to four times during the 17 d of differentiation, but was 30-35% lower in the CLA-treated cells than in the negative control cells. Compared with the negative control cells, differentiation was increased in the cells treated with C18:1 (increased Oil Red O-stained material [OROSM], triacylglycerol, glycerol 3-phosphate dehydrogenase activity [GPDH], peroxisome proliferator-activated receptor-gamma [PPAR gamma] messenger ribonucleic acid [mRNA], and lipoprotein lipase [LPL] mRNA). In effect, the C18:1-treated cells act as a positive control to demonstrate the differentiation capacity of each cell lot. Both 9,11-CLA- and 10,12-CLA-treated cells had increased differentiation (increased OROSM, triacylglycerol, GPDH, PPAR gamma, and LPL) compared with the negative control cells. The data suggest that early in differentiation when de novo fatty acid (FA) synthesis is limited and competition for FAs by membrane and triacylglycerol synthetic pathways is great, human preadipocytes do not differentiate unless a PPAR gamma ligand is added. Either CLA isomer or C18:1 can provide such a ligand.