BASIC NUTRITIONAL INVESTIGATION The 1Otrans, 12cis Isomer of Conjugated Linoleic Acid Promotes Energy Metabolism in OLETF Rats Koji Nagao, PhD, Yu-Ming Wang, PhD, Nao Inoue, BS, Seo-Young Han, PhD, Yohanes Buang, MS, Tsuneyuki Noda, MS, Noriyuki Kouda, MS, Hiroshi Okamatsu, MS, and Teruyoshi Yanagita, PhD From the Laboratory of Nutrition Biochemistry, Department of Applied Biological Sciences, Saga University, Saga, Japan; and the Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical, Co., Ltd., Shiga, Japan OBJECTIVE: We investigated the effect of conjugated linoleic acid (CLA) on energy metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: In experiment 1, male OLETF rats were fed either control diet, 10% safflower oil or CLA diet, 9% safflower oil plus 1% CLA for 4 wk. In experiment 2, male OLETF rats were fed either 9c,11t-CLA diet, 9% safflower oil plus 1% 9c,11t-CLA–rich oil or 10t,12c-CLA diet, 9% safflower oil plus 1% 10t,12c-CLA–rich oil for 10 d. RESULTS: In experiment 1, after 4 wk of feeding, serum and hepatic triacylglycerol concentrations in the CLA group were decreased significantly as compared with the control group. The CLA diet increased oxygen consumption and energy expenditure as compared with the control diet in OLETF rats. In experiment 2, a significant reduction of serum and hepatic triacylglycerol concentrations was seen in the 10t,12c-CLA group as opposed to the 9c,11t-CLA group. Oxygen consumption and energy expenditure were significantly higher in the 10t,12c-CLA group than in the 9c,11t-CLA group. CONCLUSIONS: These results demonstrated that the hypolipidemic effect and the enhancement of energy metabolism by CLA can be attributed to the effect of the 10t,12c-CLA isomer. Nutrition 2003;19: 652– 656. ©Elsevier Inc. 2003 KEY WORDS: conjugated linoleic acid isomer, Otsuka Long-Evans Tokushima Fatty rat, energy metabolism INTRODUCTION Conjugated linoleic acid (CLA) refers to a mixture of positional and geometric isomers of linoleic acid with conjugated double bonds and is found in meat and dairy products such as beef, milk, and processed cheese. 1,2 CLA has attracted considerable attention because of its potentially beneficial biological effects to inhibit carcinogenesis and to attenuate atherosclerosis in animal models. 3–5 CLA has also been reported to reduce body fat and enhance lean body mass. 6–8 Recent studies have reported that in humans dietary CLA supplementation reduces the percentage of body fat as compared with control groups. 9 –11 This effect has been attributed to the action of CLA on energy expenditure. CLA suppresses body fat accumulation and enhances the energy metabolism in mice. 12–15 However, CLA feeding increased liver weight and induced the development of fatty liver. 12,14,16 We previously reported that CLA feeding reduces body fat mass without the accumulation of lipids in the liver in obese/diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. 17,18 The OLETF rat is useful to study obesity. OLETF rats have hyperphagia, because they lack receptors for cholecystokinin, become obese, and develop hyperlipidemia and diabetes. 19 –22 We also reported that CLA enhances fatty acid -oxidation in liver, muscle, white adipose tissue, and brown adipose tissue in OLETF rats and thus may have antiobesity action. Some studies have recently suggested that different CLA iso- mers, 9c,11t-CLA and 10t,12c-CLA, have different effects on glucose and lipid metabolism. 23–26 We observed that the 10t,12c- CLA isomer, but not other isomers, reduce apolipoprotein B100 secretion in cultured human hepatoma Hep G2 cells. 27 In the present study, we studied the effect of CLA on oxygen consump- tion and evaluated the difference in the effects of 9c,11t- and 10t,12c-CLA isomers on energy expenditure in OLETF rats. MATERIALS AND METHODS Animals and Diets Four-week-old male OLETF rats were obtained from the To- kushima Research Institute (Otsuka Pharmaceutical Company Ltd., Tokushima, Japan). Rats were housed individually in metal cages in a temperature-controlled room (24°C) under a 12-h light/ dark cycle. After a 1-wk adaptation period, the rats were assigned to one of two groups (n = 6 rats/group) that were fed ad libitum with a semisynthetic diet supplemented with 10% of safflower oil (control group) or a semisynthetic diet supplemented with 9% of safflower oil and 1% of CLA (CLA group) in experiment 1. The CLA and safflower oil were provided by Rinoru Oil Mills (Nagoya, Japan). The compositions of the semisynthetic diet and fatty acids are presented in Table I. The fatty acid profile of the diets was measured with gas liquid chromatography. The animals received different diets for 4 wk. For experiment 2, 8-wk-old OLETF rats were assigned to one of two groups (n = 6 rats/group) that were fed ad libitum with a semisynthetic diet supplemented with 9% of safflower oil plus 1% of 9c,11t- CLA–rich oil (9c,11t- CLA group) or a semisynthetic diet supplemented with 9% of safflower oil plus 1% of 10t,12c-CLA–rich oil (10t,12c-CLA group). Both CLA isomer rich oils were provided by Rinoru Oil Correspondence to: Teruyoshi Yanagita, PhD, Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan. E-mail: yanagitt@cc.saga-u.ac.jp 0899-9007/03/$30.00 Nutrition 19:652– 656, 2003 ©Elsevier Inc., 2003. Printed in the United States. All rights reserved. doi:10.1016/S0899-9007(03)00060-1