Lycopene, the predominant carotenoid in tomatoes, is among the major carotenoids in serum and tissues of Americans. Although about 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues contain mainly cis-isomers. Several research groups have suggested that cis-isomers of lycopene are better absorbed than the all-trans form because of the shorter length of the cis-isomer, the greater solubility of cis-isomers in mixed micelles, and/or as a result of the lower tendency of cis-isomers to aggregate. Work with ferrets, a species that absorbs carotenoids intact, has demonstrated that whereas a lycopene dose, stomach, and intestinal contents contained 6-18% cis-lycopene, the mesenteric lymph secretions contained 77%-cis isomers. The ferret studies support the hypotheses that cis-isomers are substantially more bioavailable then all-trans lycopene. In vitro studies suggest that cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons. The implications of these findings are not yet clear. Rats appear to accumulate lycopene in tissues within the ranges reported for humans, suggesting that they can be used to study effects of lycopene isomers on disease processes. Investigations are underway to determine whether there are biological differences between all-trans and various cis-isomers of lycopene regarding its antioxidant properties or other biological functions.

Lycopene is the predominant carotenoid in tomatoes and tomato-based foods and is also a predominant carotenoid in human serum and tissues. Intake of lycopene-rich foods was recently associated with decreased risk for several chronic diseases. The observation that serum and tissue lycopene is more than 50% cis-lycopene, whereas tomatoes and tomato-based foods contain mainly all-trans-lycopene, has led to the hypothesis that cis-isomers of lycopene are more bioavailable. We tested this hypothesis both in vitro (study 1) and in vivo (study 2). In study 1, bile acid micelles containing crystalline lycopene were prepared. The crystalline lycopene used for these analyses was 54.4% cis-lycopene. The optically clear micelle preparation contained 75.9% cis-lycopene in repeated analyses. In study 2, mesenteric lymph duct cannulated ferrets were used to study the in vivo absorption of lycopene from LycoredTM (an ethyl acetate extract of tomatoes containing 5% lycopene by weight; of which 91% was all-trans lycopene). Before being anesthetized, male ferrets (n = 7) were dosed orally with 40 mg lycopene per kg body weight in soybean oil. Lymph secretions were collected, on ice, for 2 h. The residual stomach and small intestinal contents, mucosa lining, lymph secretion and serum were analyzed by HPLC. Whereas the dose, stomach and intestinal contents contained 6.2-17.5% cis-lycopene, the mesenteric lymph secretions contained significantly more, 77.4%, cis-lycopene (P < 0.01). These studies demonstrate that in ferrets, cis-isomers of lycopene are more bioavailable than trans-lycopene probably because cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons.

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Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities.

Group 1B phospholipase A2 (PLA2) is an abundant lipolytic enzyme that is well characterized biochemically and structurally. Because of its high level of expression in the pancreas, it has been presumed that PLA2 plays a role in the digestion of dietary lipids, but in vivo data have been lacking to support this theory. Our initial study on mice lacking PLA2 demonstrated no abnormalities in dietary lipid absorption in mice consuming a chow diet. However, the effects of PLA2 deficiency on animals consuming a high-fat diet have not been studied. To investigate this, PLA2(+/+) and PLA2(-/-) mice were fed a western diet for 16 wk. The results showed that PLA2(-/-) mice were resistant to high-fat diet-induced obesity. This observed weight difference was due to decreased adiposity present in the PLA2(-/-) mice. Compared with PLA2(+/+) mice, the PLA2(-/-) mice had 60% lower plasma insulin and 72% lower plasma leptin levels after high-fat diet feeding. The PLA2(-/-) mice also did not exhibit impaired glucose tolerance associated with the development of obesity-related insulin resistance as observed in the PLA2(+/+) mice. To investigate the mechanism by which PLA(2)(-/-) mice exhibit decreased weight gain while on a high-fat diet, fat absorption studies were performed. The PLA(2)(-/-) mice displayed 50 and 35% decreased plasma [(3)H]triglyceride concentrations 4 and 6 h, respectively, after feeding on a lipid-rich meal containing [(3)H]triolein. The PLA(2)(-/-) mice also displayed increased lipid content in the stool, thus indicating decreased fat absorption in these animals. These results suggest a novel role for PLA(2) in the protection against diet-induced obesity and obesity-related insulin resistance, thereby offering a new target for treatment of obesity and diabetes.

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