| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Conjugated linoleic acid (CLA) has attracted considerable attention because of its physiological functions, however, feeding a CLA mixture and the 10trans, 12cis-CLA isomer with a low-fat diet induced lipodystrophy in mice.
First, we investigated the effect of short-term feeding of CLA on adipose tissue weights, liver weight, hepatic lipid metabolism, and serum lipoprotein profiles in C57BL/6J mice. Mice were fed semi-synthetic diets containing either 6% high-linoleic safflower oil (HL-SAF) or 4% HL-SAF+2% CLA for 1 wk. Short-term feeding of CLA showed an anti-obesity effect without inducing hepatomegaly in mice. In addition to the decline of hepatic triglyceride concentration, significant inhibition of. 9 desaturation of fatty acid in the total liver lipids was found in CLA-fed mice. The CLA diet significantly increased the activities of peroxisomal b-oxidation and decreased the activities of diacylglycerol acyltransferase, a triglyceride synthesis-related enzyme, in the liver. Moreove
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r, serum lipoprotein profiles of CLA-fed mice showed preferable changes in the atherogenic indices. However, serum leptin and adiponectin were drastically decreased by CLA feeding, suggesting that prolonged administation of CLA would induce further decrease of serum adipocytokine levels, which may be a cause of lipodystrophy in mice.
Next, we investigated the effect of dietary combination of CLA and docosahexaenoic acid (DHA) to attenuate CLA induced fatty liver in C57BL/6N mice. Mice were fed semi-synthetic diets that contained either 6% high linoleic safflower oil (HL-SAF), 4% HL-SAF+2% CLA, or 3.5% HL-SAF+2% CLA+0.5% DHA for 4 wk. This 4-wk feeding of CLA showed hepatic lipid accumulation concomitant with the decrease in adipose tissue weight in mice However, 0.5% supplementation of DHA to the CLA diet could alleviate fatty liver without decreasing the anti-obesity effect of CLA. The CLA diet promoted fatty acid synthesis in the liver, but DHA supplementation significantly attenuated the increase in enzyme activity induced by CLA. On the other hand, serum adipocytokines, leptin and adiponectin, were drastically decreased by CLA feeding, and DHA supplementation did not affect those levels.
These results show that CLA does not directly induce hepatic steatosis in mice and insulin-resistance, and that combination of dietary components with CLA can attenuate CLA-induced fatty liver through the regulation of heptic lipid metabolism in mice. Less
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