Structure-activity relationship of conjugated linoleic acid and its cognates in inhibiting heparin-releasable lipoprotein lipase and glycerol release from fully differentiated 3T3-L1 adipocytes

Conjugated linoleic acid (CLA) reduces body fat in part by inhibiting the activity of heparin-releasable lipoprotein lipase (HR-LPL) activity in adipocytes, an effect that is induced by the trans-10,cis-12 CLA isomer. In this study we used a series of compounds that are structurally related to CLA (i.e., CLA cognates) to investigate the structural basis for this phenomenon. None of the 18:1 CLA cognates that were tested, nor trans-9,cis-12 18:2, cis-12-octadecen-10-ynoic acid (10y,cis-12) or 11-(2'-(n-pentyl)phenyl)-10-undecylenic acid (designated P-t10), exhibited any significant effect on HR-LPL activity. Among the CLA derivatives (alcohol, amide, and chloride) that were tested, only the alcohol form inhibited HR-LPL activity, although to a lesser extent than CLA itself. In addition, intracellular TG was reduced only by trans-10,cis-12 CLA and the alcohol form of CLA. Hence it appears that the trans-10,cis-12 conjugated double bond in conjunction with a carboxyl group at C-1 is required for inhibition of HR-LPL activity, and that an alcohol group can partially substitute for the carboxyl group. We also studied glycerol release from the cells, observing that this was enhanced by trans-10 18: 1, trans-13 18: 1, cis-12 18:1, cis-13 18:1, P-t10 but was reduced by cis-9 18:1, the alcohol and amide forms of CLA or 10y,cis-12. Accordingly the structural feature or features involved in regulating lipolysis appear to be more complex. Despite enhancing lipolysis in cultured 3T3-L1 adipocytes, trans-10 18:1 did not reduce body fat gain when fed to mice. (C) 2004 Elsevier Inc. All rights reserved.