Joseph A. Scimeca

Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.

Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake

Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice ( n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice (n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.

Conjugated linoleic acid. A powerful anticarcinogen from animal fat sources

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid, which is found preferentially in dairy products and meat. Preliminary studies indicate that CLA is a powerful anticarcinogen in the rat mammary tumor model with an effective range of 0.1‐1% in the diet. This protective effect of CLA is noted even when exposure is limited to the time of weaning to carcinogen administration. The timing of this treatment corresponds to maturation of the mammary gland to the adult stage, suggesting that CLA may have a direct effect in reducing the cancer risk of the target organ. Of the vast number of naturally occurring substances that have been demonstrated to have anticarcinogenic activity in experimental models, all but a handful of them are of plant origin. Conjugated linoleic acid is unique because it is present in food from animal sources, and its anticancer efficacy is expressed at concentrations close to human consumption levels.

Effect of timing and duration of dietary conjugated linoleic acid on mammary cancer prevention

Conjugated linoleic acid (CLA) is a minor fatty acid found predominantly in the form of triglycerides in beef and dairy products. Previous work by Ip and co-workers showed that free fatty acid-CLA at < or = 1% in the diet is protective against mammary carcinogenesis in rats. The present study verified that the anticancer activities of free fatty acid-CLA and triglyceride-CLA are essentially identical. This is an important finding, because it rules out a nonspecific free fatty acid effect. In terms of practical implication, we can continue the in vivo research with the less-expensive free fatty acid-CLA without compromising the physiological relevance of the data. A primary objective of this report was to investigate how the timing and duration of CLA feeding might affect the development of mammary carcinogenesis in the methylnitrosourea (MNU) model. We found that exposure to 1% CLA during the early postweaning and pubertal period only (from 21 to 42 days of age) was sufficient to reduce subsequent tumorigenesis induced by a single dose of MNU given at 56 days of age. This period incidentally corresponds to a time of active morphological development of the mammary gland to the mature state. In contrast to the above observation, a continuous intake of CLA was required for maximal inhibition of tumorigenesis when CLA feeding was started after MNU administration, suggesting that some active metabolite(s) of CLA might be involved in suppressing the process of neoplastic promotion/progression.

Conjugated linoleic acid and linoleic acid are distinctive modulators of mammary carcinogenesis

Previous work by Ip and co-workers showed that mammary cancer prevention by conjugated linoleic acid (CLA) is independent of the level of fat in the diet. Because CLA is an isomer of linoleic acid, there is the question regarding whether the effect of CLA is due to a displacement of linoleic acid in cells. To further evaluate whether there might be an interaction between linoleic acid and CLA, the present study was designed to examine the dose response to CLA (at 0.5%, 1%, 1.5%, and 2%) in rats fed a 2% or a 12% linoleate diet (both basal diets contained 20% total fat by weight). The end points of investigation included the bioassay of mammary tumorigenesis in the rat dimethylbenz[a]anthracene model as well as the incorporation of CLA, linoleic acid, and arachidonic acid in mammary glands. The mammary carcinogenesis results showed that the efficacy of tumor suppression by CLA was not affected by linoleate intake. With either linoleate diet, no further protection was evident with levels of CLA > 1%. Analysis of neutral lipids and phospholipids of the mammary tissue indicated that 1) the accumulation of CLA in mammary tissue was dose dependent from 0.5% to 2%, 2) CLA concentration was 10 times higher in neutral lipids than in phospholipids, 3) the incorporation of CLA in either fraction was not affected by the availability of linoleic acid, and 4) CLA did not appear to displace linoleic acid or arachidonic acid in the mammary tissue. The above findings suggest that there may be distinctive mechanisms in the modulation of tumor development by linoleic acid and CLA.

Potential Health Benefits of Conjugated Linoleic Acid

This supplement to the Journal of the American College of Nutrition contains papers that were presented in a symposium entitled Health Benefits of Conjugated Linoleic Acid , which was held on October 2, 1999, in Washington, D.C., as part of the 40th Annual Meeting of the American College of Nutrition. The symposium organizers sought to provide a forum in which to present and discuss the latest research about the potential human health benefits of consuming diets high in conjugated linoleic acid (CLA) to health professionals practicing in the fields of general and clinical nutrition. Although all the data presented at the meeting were based on laboratory animal investigations, the implications for human health are readily apparent and far-reaching. Presently, CLA is a term used to denote a group of isomers of linoleic acid (cis-9, cis-12-octadecadienoic acid). The characteristic that binds these isomers together is that, unlike linoleic acid, the two double bonds along the 18-carbon fatty acid chain are not separated by a methylene carbon and, hence, are termed “conjugated.” Of the many positional and geometric isomers of CLA that are possible, the cis-9, trans-11-octadecadienoic acid isomer predominates in food products [1]. This isomer is naturally rich in milk fat, being produced by rumen bacteria during the process of biohydrogenation. The reader is encouraged to read Griinari and Bauman [2] for a review of the biosynthesis of CLA. The history of conjugated linoleic acid extends back to the 1930s, when the presence of fatty acids obtained from butter fat was reported to exhibit spectrophotometric absorption at 230 mm, thus indicating the presence of two conjugated double bonds. It was not until the advent of gas liquid chromotography, that Peter Parodi and others were able to fractionate the methyl esters of milk fat and hence were able to quantitatively determine some of the isomers of CLA, including the cis-9, trans-11-octadecadienoic acid isomer, which has the proposed name of rumenic acid. For an excellent historical summary of the discovery of CLA in milk fat, the reader is referred to a review by Parodi [3]. The turning point in CLA research can be traced back to investigations by Michael Pariza that revealed the presence of “mutagenesis inhibitory” activity in extracts of grilled ground beef [4]. Subsequent research established that the extract exhibited anticarcinogenesis activity as well [5] and that the identity of the active principle was CLA [6]. These studies have led to hundreds of investigations and the recognition of multiple biological effects of CLA. The symposium organizers selected five areas of CLA research to highlight in the symposium: inhibition of mammary cancer, retardation and regression of atherosclerosis, modification of body fat metabolism and partitioning, anti-diabetic effect and enhancement of bone formation. This supplemental section includes three of the five papers presented at the symposium. Not included in the supplement are papers by Drs. Clement Ip and Karen Houseknecht. Both investigators have recently published papers that include much of the material they presented during the symposium. Clement Ip’s presentation focused on research which demonstrated for the first time that naturally-occurring CLA in a food form had biological activity and that this activity was similar to that produced by a mixture of CLA isomers delivered as free fatty acids [7]. Karen Houseknecht’s research extends to the original observation of an anti-diabetic effect by dietary CLA using the Zucker diabetic fatty rat model [8], and her presentation included research that was recently published on the mode of action(s) by which CLA was responsible for the anti-diabetic effect [9–11]. The first of the papers in this supplement is by David Kritchevsky and contains research that examined the effect of CLA on the establishment and progression of atherosclerosis in rabbits. It is interesting to note that Dr. Kritchevsky’s research provides evidence that not all trans fatty acids may similarly contribute to cardiovascular disease. The next paper is authored by Drs. Bruce Watkins and Mark Seifert and reviews bone biology and the effects of dietary factors such as CLA on bone metabolism. The last paper is by Dr. James DeLany and colleagues and examines changes in body composition with CLA consumption.

Effect of Conjugated Linoleic Acid on Carcinogenesis

Conjugated linoleic acid (CLA) refers to a mixture of positional and geometric isomers of linoleic acid. The two double bonds in CLA are primarily in positions 9 and 11, or 10 and 12, along the carbon chain, thus giving rise to the designation of a conjugated diene. Each of the double bonds can be in the cis or {trans} configuration, and hence eight isomers are formed from the isomerization of linoleic acid.