- AMPK Activator AICAR Inhibits Hepatic Gluconeogenesis and Fatty Acid Oxidation.
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Jin Yob Kim, Eun Hee Koh, Woo Je Lee, Seong Min Han, Ji Young Youn, Hye Sun Park, Hyun Sik Kim, Min Seon Kim, Joong Yeol Park, Ki Up Lee
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Korean Diabetes J. 2005;29(1):6-14. Published online January 1, 2005
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 Abstract
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- BACKGROUND
Recent studies have demonstrated that adiponectin and metformin activate AMPK in the liver, and adiponectin and metformin stimulate fatty acid oxidation while inhibiting glucose production in liver. These results are in contrast to previous studies that have demonstrated that increased fatty acid oxidation in the liver is associated with increased gluconeogenesis. The present study was undertaken to reinvestigate the effects of AMPK activation by AICAR on hepatic fatty acid oxidation and gluconeogenesis. METHODS: HePG2 cells were treated with various concentrations of AICAR, and then the fatty acid oxidation and gluconeogenesis of the cells were determined. To investigate the in vivo effect of AICAR, Sprague-Dawely rats were infused with AICAR (bolus, 40 mg/g; constant, 7.5 mg/g/min-1) for 90min. RESULTS: Incubation of the HePG2 cells with higher concentrations (=1 mM) of AICAR increased fatty acid oxidation and gluconeogenesis. On the other hand, incubation of HePG2 cells with lower concentrations (0.05 and 0.1 mM) of AICAR decreased fatty acid oxidation and gluconeogenesis. Consistent with this in vitro data, the intravenous administration of AICAR to rats lowered their plasma glucose concentration and inhibited hepatic gluconeogenesis. Fatty acid oxidation in the liver tissue was significantly decreased by the administration of AICAR. CONCLUSION: The present study has demonstrated that AICAR decreased gluconeo-genesis in the liver. In contrast to previous studies, AICAR profoundly decreased hepatic fatty acid oxidation in rats and also in cultured hepatocytes
- Anti-obesity Effects of alpha-lipoic Acid in OLETF Rats.
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Kee Ho Song, Ji Young Youn, Chul Nam Koong, Min Jeong Shin, Jae Won Ryu, Hye Sun Park, Min Seon Kim, Joong Youl Park, Ki Up Lee
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Korean Diabetes J. 2002;26(6):460-468. Published online December 1, 2002
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Abstract
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- BACKGROUND
Obesity is closely related to the development of type 2 diabetes mellitus, hypertension and cardiovascular disease. While the prevalence of obesity is rapidly increasing in most parts of the world, its effective treatment is not available due to the limited efficacy, and the side effects, of anti-obesity drugs. We unexpectedly found that administration of alpha-lipoic acid (ALA) resulted in a significant reduction in the body weight of rodents. This study aimed to investigate the mechanisms of the anti-obesity effect of ALA in the obese diabetic models of Otsuka Long Evans Tokushima (OLETF) rats. MATERIALS AND METHODS: Ten weeks old male OLETF rats were randomly assigned into one of three groups (n=6 per group): 1) the control group, fed with normal rat chow 2) the ALA group, fed with rat chow containing ALA (0.5% of food weight) and 3) the pair-fed group, fed with normal rat chow, but given the same amount of food as consumed by the ALA group. The body weight and food intakes were monitored for 3 weeks. At the end of the study, abdominal CT scans were performed to measure the visceral fat content. The energy expenditure and respiratory quotient were measured on days 3, 9 and 21 using an indirect calorimeter. The expression of the uncoupling protein-1 mRNA in the white and brown adipose tissues were determined by Northern blot analyses. The oxidation of fatty acids in the skeletal muscle, liver and adipose tissue was also measured. RESULTS: The administration of ALA induced a significant weight loss and reduction in food intake throughout the study period. The weight loss in the ALA group was greater than in the pair-fed group (p<0.05), suggesting an enhanced energy metabolism in the ALA group. In the ALA treated animals, the energy expenditure was significantly increased together with an elevated expression of UCP-1 mRNA in the brown, and an ectopic expression of UCP-1 mRNA in the white adipose tissues. The oxidation of fat in the brown adipose tissue and skeletal muscle was also increased after the ALA treatment, which was in line with the reduced respiratory quotient in the ALA group. The abdominal CT scan revealed a reduction in the visceral fat content in the ALA group compared to the control group. CONCLUSION: The present study demonstrated, for the first time, a novel anti-obesity action of ALA in obese OLETF rats, which proceeds through at least three different mechanisms: 1) reduction in food intake, 2) increase in energy expenditure and 3) enhancement of fat oxidation.
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