• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.181-186
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• 2012

Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

• 대한임상검사과학회지
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• 제36권2호
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• pp.215-221
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• 2004

To determine the effects of caloric restriction on obese type 2 diabetes we measured body blood glucose and serum lipid level in dietary restricted Otsuka Long Evans Tokushima Fatty (OLETF) rats. OLETF rats (obese diabetic rats) and Long Evans Tokushima Otsuka (LETO) rats (control rats) were grouped into 2 groups; control (free feed) group and 30% caloric restricted (30% CR) group. At 24 weeks of age the 30% CR animals were provided a diet at a level of 30% less food (by weight) than control rats consumed during the previous week. Blood glucose levels and serum triglyceride, total cholesterol, and high density lipoprotein (HDL)-cholesterol levels of CR rats were determined every 2 weeks for 8 weeks total. Blood glucose, triglyceride and total cholesterol levels of OLETF rats were significantly higher compared to LETO rats. In OLETF rats, the blood glucose levels were decreased to 61% by 8 weeks in the 30% CR compared to the non-CR control group, but changes of blood glucose levels were not observed in LETO rats during the 8weeks in the 30% CR. The serum triglyceride levels of OLETF rats were decreased significantly in the 30% CR but no change in the serum of LETO rats was found. The total cholesterol level was not changed by dietary restriction in LETO rats, but significant changes were observed in OLETF rats by 30% dietary restriction. HDL-cholesterol levels were also increased by dietary restriction in both LETO and OLETF rats. These results suggested that elevated blood glucose, triglyceride and total cholesterol levels in diabetes II patients may be reduced by caloric restriction.

• Food Science and Biotechnology
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• 제15권1호
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• pp.122-127
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• 2006

The effects of fermented chaga mushroom (Inonotus obliquus) powder on the lipid concentrations and the activities of liver marker enzymes of serum in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats were investigated. Rats were fed a semisynthetic diet supplemented with 50 g/kg chaga mushroom powder (CM) or 50 g/kg fermented chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age). Nondiabetic Long-Evans Toknshima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. Water consumption was significantly higher in the OLETF control than the LETO rats. Water consumption in the FCM-fed OLETF rats tended to be less than in both the OLETF control and CM-fed OLETF rats. Serum concentrations of triglycerides and total cholesterol were significantly higher in the OLETF control rats than in the LETO rats while within the OLETF rat groups, the consumption of FCM resulted in a significantly lower serum triglyceride concentration and slightly lowered serum total cholesterol concentration when compared to the OLETF control and CM-fed rats. The alanine aminotransferase (ALT) activity was significantly higher in the OLETF control than in the LETO rats, but this difference was significantly reduced compared to the CM-fed rats and essentially no difference in the ALT levels was observed between the LETO and OLETF-FCM rats. This observation suggests an adaptive effect of the fermented chaga mushroom in liver function. Livers of the LETO rats showed no histopathological changes, whereas those of the OLETF control rats were characterized by many fat depositions in the central zone of the hepatocytes. The livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF control rats and fat deposition in the hepatocytes was nearly absent. These results suggest that orally ingested fermented chaga mushroom has a potential beneficial effect on the complications known to occur in the obesity-related non-insulin dependent diabetes mellitus (NlDDM) OLETF rat.

• The Korean Journal of Physiology and Pharmacology
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• 제14권2호
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• Food Science and Biotechnology
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• 제15권5호
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• pp.739-745
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• 2006

Changes in the levels of analytes in the blood and urine of a rodent animal model were taken as a measure of the hypoglycemic effects of a diet containing fermented chaga mushroom. These studies were conducted using the genetically manipulated diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The effects of 8-week long diets that included either fermented (FCM) or non-fermented (CM) chaga mushroom powder (5% in the diet) on the OLETF rat were compared to the normal diet fed OLETF rat and the non-diabetic Long-Evans Tokushima Otsuka (LETO) rat. Hypoglycemia was tracked by measuring serum and urine concentrations of glucose, insulin, fructosamine, and leptin. Serum and urine levels of glucose, fructosamine, and leptin in the OLETF rats were higher than in LETO rats when fed normal diets but insulin levels did not differ between the two animal groups. The FCM rats were characterized by dramatically low levels of serum glucose and leptin in the OLETF rats whereas the levels of fructosamine and urine glucose trended lower in response to FCM. The serum leptin level in the CM-fed OLETF rat was also lower than that in the normal diet fed OLETF control. Serum concentrations of insulin in the OLETF rats were higher following FCM or CM feeding compared to the normal diet. These observations imply that (a) a dietary supplement of fermented chaga mushroom may contribute to a hypoglycemic effect in the OLETF rat, and (b) the increased blood insulin concentration following 8 weeks of an FCM diet may be important to the noted improvement in hyperglycemia.

• 한국식품영양과학회지
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• 제30권6호
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• pp.1210-1214
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• 2001

본 실험은 식이 제한 급여에 따른 비만형 당뇨병 환자의 체중 및 혈중 지질량의 변화에 대한 연구의 일환으로 사람의 비만형 당뇨병과 유사한 병리소견을 나타내는 OLETF 횐쥐를 이용하여 자유급식군, 식이 급여량 20% 제한군과 식이 급여량 40% 제한군으로 나누어 12주간 사육한 후 체중과 혈당, 혈청 콜레스테롤 및 중성지질량을 측정하여 식이 제한 급여 에 따른 혈청 지질량의 변화를 관찰하였다. LETO 횐쥐에서 자유급식군은 12주 후 체중이 41% 증가되었으나 식이 급여량 20% 제한군은 22%, 식이 급여량 40% 제한군은 10%의 체중 증가를 나타냈고, OLETF 횐쥐에서 자유급식군은 24%, 식이 급여량 20% 제한군은 10%, 식이 급여량 40% 제한군은 -2%의 체중 증가를 나타냈다. 혈당량은 LETO 흰쥐에서 식이 급여량 20% 제한군은 혈당량이 감소되지 않았으나, 식이 급여량 40% 제한군은 12% 감소되고, OLETF 횐쥐 혈당량은 식이 급여량 20% 제한군은 15%, 식이 급여량 40% 제한군은 20%가 감소되었다. 혈청 중성지질량은 LETO흰쥐에서 식이 급여량 20% 제한군은 24%, 식이 급여량 40% 제한군은 27%가 감소되었고, OLETF 횐쥐에서는 식이 급여량 20% 제한군은 32%, 식이 급여량 40% 제한군은 37% 정도가 각각 감소되었다. 혈청 총 콜레스테롤량은 LETO 횐쥐에서는 자유급식군, 식이 급여량 20% 제한군과 식이 급여량 40% 제한군에서 모두 차이를 나타내지 않았고, OLETF 횐쥐에서는 식이 급여량 20% 제한군은 15%, 식이 급여량 40% 제한군은 23% 정도가 감소되었다. HDL-콜레스테롤량은 LETO 흰쥐에서 식이 급여량 20% 제한군은 34%, 식이 급여량 40% 제한군은 43%가 증가되었다. 이상의 실험결과로서 식이 제한 급여에 의한 체중, 혈당, 혈청 지질량의 변화가 OLETF 횐쥐에서 LETO 횐쥐에서 보다 더 유의한 것으로 나타나서, 식이 제한 급여에 의한 혈청 중성지질량과 혈청 총콜레스테롤 및 HDL-콜레스테롤량의 변화는 당뇨병에서 더 큰 변화가 유발되는 것으로 추측된다.