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Trans ‐10, Cis ‐12 conjugated linoleic acid reduces triglyceride content while differentially affecting peroxisome proliferator activated receptor γ2 and aP2 expression in 3T3‐L1 preadipocytes
Author(s) -
Evans M.,
Park Y.,
Pariza M.,
Curtis L.,
Kuebler B.,
McIntosh M.
Publication year - 2001
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-001-0836-z
Subject(s) - conjugated linoleic acid , adipogenesis , linoleic acid , triglyceride , peroxisome proliferator activated receptor , fatty acid , adipose tissue , chemistry , peroxisome proliferator activated receptor gamma , peroxisome , phospholipid , clinical chemistry , medicine , 3t3 l1 , lipidology , biochemistry , receptor , endocrinology , biology , cholesterol , membrane
A series of experiments was conducted using 3T3‐L1 preadipocytes as the cell model to determine: (i) whether the triglyceride (TG)‐lowering effects of a crude mixture of conjugated linoleic acid (CLA) isomers were due to a specific isomer of CLA and the timing of treatment, (ii) if CLA reduced TG content by inhibiting a key regulator of adipogenesis, (iii) if CLA incorporated into either neutral lipid or phospholipid cell fractions, and (iv) whether the effects of CLA treatment were reversible. Trans ‐10, cis ‐12 CLA reduced TG content, whereas the cis ‐9, trans ‐11 isomer increased TG content compared to vehicle [bovine serum albumin (BSA)] controls. Treatment with 50 μM trans ‐10, cis ‐12 CLA during the entire 6 d of differentiation reduced TG content to a greater extent than treatment during either the first 3 d or last 3 d of differentiation. Trans ‐10, cis ‐12 CLA treatment of preadipocyte cultures for 48 h increased peroxisome proliferator activated receptor γ2 (PPARγ2) protein expression compared to cultures treated with linoleic acid (LA) or the BSA controls. CLA had no effect on adipose P2 (aP2), a fatty acid‐binding protein regulated by PPARγ2. Both the cis ‐9, trans ‐11 and the trans ‐10, cis ‐12 isomers of CLA were incorporated into neutral lipids and phospholipids. However, cis ‐9, trans ‐11 CLA levels were one‐ to twofold higher than trans ‐10, cis ‐12 CLA levels. Moreover, trans ‐10, cis ‐12 CLA treatment reduced cis ‐11 18∶1 concentrations in both neutral lipids and phospholipids while increasing cis ‐9 18∶1 and 18∶2 concentrations. Palmitoleic acid (16∶1) levels were also lower in the neutral lipid fraction of cultures treated with trans ‐10, cis ‐12 CLA. Supplementing trans ‐10, cis ‐12 CLA‐treated cultures (50 μM) with increasing levels of LA resulted in a dose‐dependent increase in TG content compared to cultures treated with 50 μM CLA alone. LA supplementation also prevented some of the morphological changes associated with trans ‐10, cis ‐12 CLA treatment as seen with scanning electron microscopy. Treatment with 50μM trans ‐10, cis ‐12 CLA for 6 d decreased PPARγ2 levels, and supplementation of CLA‐treated cultures with LA increased PPARγ2 levels compared with cultures treated with CLA alone. Taken together, these data indicate that in cultures of 3T3‐L1 preadipocytes: (i) trans ‐10, cis ‐12 CLA is the TG‐lowering isomer of CLA, and its effects are dependent on dose, duration of treatment, and the amount of LA in the cultures; (ii) trans ‐10, cis ‐12 CLA treatment alters the monounsaturated fatty acid profile of neutral‐ and phospholipids of the cultures; and (iii) although acute (2−d) trans ‐10, cis ‐12 CLA treatment increased PPARγ2 protein levels, chronic (6−d) treatment decreased PPARγ2 levels.