Review
The biologically active isomers of conjugated linoleic acid

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Abstract

Numerous physiological effects are attributed to conjugated linoleic acid (CLA). The purpose of this presentation is to consider these effects with respect to the cis-9,trans-11 and trans-10,cis-12 CLA isomers. We review previously published data and present new findings that relate to underlying biochemical mechanisms of action. Both isomers are natural products. The cis-9,trans-11 isomer is the principal dietary form of CLA, but the concentrations of this isomer and the trans-10,cis-12 isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The trans-10,cis-12 CLA isomer exerts specific effects on adipocytes, in particular reducing the uptake of lipid by inhibiting the activities of lipoprotein lipase and stearoyl–CoA desaturase. The trans-10,cis-12 CLA isomer also affects lipid metabolism in cultured Hep-G2 human liver cells, whereas both the cis-9,trans-11 and trans-10,cis-12 CLA isomers appear to be active in inhibiting carcinogenesis in animal models. We present new findings indicating that the cis-9,trans-11 CLA isomer enhances growth and probably feed efficiency in young rodents. Accordingly, the effects of CLA on body composition (induced by trans-10,cis-12 CLA) and growth/feed efficiency (induced by cis-9,trans-11 CLA) appear to be due to separate biochemical mechanisms. We also show that a 19-carbon CLA cognate (conjugated nonadecadienoic acid, CNA) inhibits lipoprotein lipase activity as effectively as CLA in cultured 3T3-L1 adipocytes. Presumably, CNA is metabolized differently than the 18-carbon CLA isomers, so this finding indicates direct activity of the administered compound as opposed to acting via a metabolite.

Introduction

Numerous fatty acids with conjugated double bonds occur naturally in edible fats derived from ruminant animals, for example milkfat and beef tallow [1], [2], [3]. Similar structures are generated when linoleic acid is heated in base [4]. The term conjugated linoleic acid and its acronym CLA refer generically to this class of positional and geometric conjugated dienoic isomers of linoleic acid, two of which (cis-9,trans-11 and trans-10,cis-12 CLA) are known to possess biological activity (Fig. 1) [5].

Prior to 1987 scientific interest in CLA was confined largely to rumen microbiologists who studied the cis-9,trans-11 CLA isomer as an intermediate in the biohydrogenation of linoleic acid [6], [7]. This changed when Ha et al. [8] reported that CLA produced by base-catalyzed isomerization of linoleic acid was an effective inhibitor of benzo(a)pyrene-initiated mouse epidermal neoplasia. Since then numerous biological and physiological effects of CLA have been reported [5], [9] (for a regularly updated listing of the scientific literature on CLA since 1987 see the Internet address http://www.wisc.edu/fri/clarefs.htm).

Recently we reviewed evidence for CLAs multi-functionality and its implications regarding possible biochemical mechanisms [5]. Emerging evidence indicates that the cis-9,trans-11 and trans-10,cis-12 CLA isomers produce different effects. Given the structural differences between these isomers it is most unlikely that a single biochemical mechanism underlies these effects. In fact, there is evidence indicating that more than one biochemical mechanism is involved in the specific effects of the trans-10,cis-12 CLA isomer [5].

Section snippets

Biosynthesis

Parodi [6] summarized the early literature describing the seasonal fluctuation of conjugated dienes (now recognized as CLA) in cow’s milk. The amounts in spring and summer (when cows were pastured) were substantially higher than in fall and winter (when cows were stall-fed). Parodi [10] established that cis-9,trans-11 CLA was the principal CLA isomer in milkfat, a finding that has been confirmed [1], [2], [3].

Dhiman et al. [11], [12], [13] studied the effect of diet on the CLA content of cow’s

Physiological effects

Numerous seemingly beneficial physiological effects have been attributed to CLA including inhibiting chemically induced carcinogenesis in several rodent models [8], [29], [30], [31], enhancing the immune response while reducing the catabolic effects of immune stimulation in rodents and chickens [32], [33], reducing atherosclerosis in rabbits [34] and hamsters [35], enhancing growth of rats [36] and pigs [37], reducing body fat gain in mice [27], [38], [39], [40], [41], [42], rats [43], [44],

Summary and conclusions

We have discussed many of the reported physiological effects of CLA with specific regard to the separate and/or synergistic actions of the two known biologically active isomers,cis-9,trans-11 and trans-10,cis-12 CLA. Previously published data were reviewed and new findings that relate to underlying biochemical mechanisms of action were presented.

Both the cis-9,trans-11 and trans-10,cis-12 CLA isomers occur naturally in food. The cis-9,trans-11 isomer is the principal dietary form of CLA, but

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