Biological activities of conjugated CLA participates in the modulation of the immune

R .J.B. Bessa et al. Livestock Production Science 63 2000 201 –211 203 rumenic acid. Contrary to what is observed with hamsters Nicolosi et al., 1997 fed atherogenic mixed conjugated octadienoic acids, Lee et al. diets. 1998 demonstrated that rumenic acid alone does Ha et al. 1990 claimed that CLA was effective not inhibit the expression of stearoyl-CoA desaturase preventing peroxide formation from unsaturated fatty mRNA. acids, although nothing in the structure of CLA Like all conjugated dienes, CLA absorbs UV light suggest that it can possess such antioxidant activity. at 234nm. This allows it to be detected by UV These authors hypothesised that an oxidised deriva- spectrophotometry Riel, 1963. This property has tive of CLA formed by the introduction of a b- been extensively used to study the peroxidation of hydroxy acrolein moiety across the conjugated doub- unsaturated fatty acids in biological systems because le-bound system is the active antioxidant species of the characteristic formation of conjugated diene rather than CLA itself. In later revaluations, van den fatty acid hydroperoxides Logani and Davies, Berg et al. 1995 and Banni et al. 1998 concluded 1980. Conjugated unsaturation in both types of that CLA has only a minor effect preventing linoleic compounds causes difficulties in interpreting peroxi- acid oxidation, that was attributed to a competition dation data measured by this method Banni et al., effect, due to the higher susceptibility of CLA to 1998, particularly when CLA content is high. oxidation. Some works even suggest that CLA can be a pro-oxidant agent Schonberg and Krokan, 1995; Chen et al., 1997.

3. Biological activities of conjugated CLA participates in the modulation of the immune

octadecadienoic acids system, enhancing the mitogen-induced lymphocyte blastogenesis, lymphocyte cytotoxic activity and The role of CLA in animal metabolism is currently macrophage killing ability Michal et al., 1992; under strong investigation. The already known ef- Chew et al., 1997; Wong et al., 1997. CLA reduces fects can be very diverse, and are not fully integrated catabolic effects in skeletal muscles in birds, rats and into a comprehensive framework of knowledge. The mice after immune stimulation, without compromis- interest of the scientific community was triggered by ing the efficacy of the immune response Cook et al., the accidental discovery of anticarcinogenic activity 1993; Miller et al., 1994. The proposed mechanism in fried beef extracts Pariza and Hargraves, 1985 in to explain this action involves the reduction of which Ha et al. 1987 later isolated CLA isomers as prostaglandin E PGE synthesis Cook et al., 2 2 being responsible for the anticarcinogenic action. 1993. The inhibitory effects of CLA on PGE were 2 Since then, the inhibitory action of CLA on several confirmed in several tissues and experimental con- chemical induced carcinogenesis models was demon- ditions Liu and Belury, 1997; Sugano et al., 1997; strated, including epidermal Ha et al., 1987; Belury Li and Watkins, 1998; Liu and Belury, 1998. The et al., 1996, mammary Ip et al., 1991, 1994b; modulation of the eicosanoid synthesis by CLA Thompson et al., 1997 and gastrointestinal car- probably includes the elongation and desaturation cinomas Ha et al., 1990; Liew et al., 1995. of CLA resulting in the synthesis of conjugated Physiological concentrations of CLA inhibits prolif- eicosatrienoic and eicosatetraenoic metabolites eration of several human cancer cell lines in vitro Banni et al., 1996. These metabolites were found in Shultz et al., 1992a,b; Schonberg and Krokan, phospholipids of the ovine hepatocyte Banni et al., 1995. Anticarcinogenic effects of CLA appear to be 1996 and in the liver Sebedio et al., 1997 and dose dependent, from 0.1 to 1 in the diet Ip et al., mammary gland Thompson et al., 1997 of rats fed 1991, 1994b. When extrapolated to humans, this CLA supplemented diets. range of concentrations is only slightly higher than Experiments with pigs Dugan et al., 1997 and the estimated consumption of CLA in the USA mice Park et al., 1997 fed a CLA supplemented population Ip et al., 1994a. diet, suggest that CLA can act as a fat to lean Dietary CLA supplementation reduces the plasma repartitioning agent. A similar effect was observed concentration of low density lipoproteins and inhibits by Chin et al. 1994a in rats. This effect on fat to atherosclerosis onset in rabbits Lee et al., 1994 and lean repartition apparently results from the reduced 204 R .J.B. Bessa et al. Livestock Production Science 63 2000 201 –211 lipogenesis and increased lipolysis in adipose tissue developed for the large scale synthesis of CLA Park et al., 1997. Furthermore, West et al. 1998 which may allow the production of CLA rich meat concluded that in mice fed high-fat and low-fat CLA and eggs through feeding regimes containing these supplemented diets, CLA reduces body fat by de- synthesised CLA’s. In monogastrics, the inclusion of creasing feed intake, by increasing metabolic rate CLA in diets is particularly promising because its and by decreasing the night-time respiratory quot- products have low CLA content and hydrogenation is ient. This lipid catabolic response is in agreement minimal in the gastrointestinal tract. Kramer et al. with observations by Belury et al. 1997, suggesting 1998b introduced 1 of a CLA commercial mix that CLA acts as a typical hepatic peroxisome into pig diets which resulted in the enrichment of proliferator. Besides the effects on lipid metabolism, meat lipids with the isomers present in the mix. the proposed reduction of PGE synthesis in skeletal 2 muscles induced by CLA Cook et al., 1993 may result in reduced proteolysis Rodemann and Gold-

5. Rumen biohydrogenation and CLA synthesis