J Korean Diabetes Assoc JKDA The Journal of Korean Diabetes Association 1015-6461 Korean Diabetes Association 10.4093/jkda.2006.30.3.161 Original Article Effects of Caloric Restriction on the Expression of PGC-1 and PPARs mRNA in Liver of Otsuka Long-Evans Tokushima Fatty Rats Kim Sang-Yong Kim Jin-Hwa Bae Hak-Yeon Lee Byoung-Rai 1 Division of Endocrinology, Department of Internal Medicine, College of Medicine, Chosun University, Korea. Department of Biochemistry, College of Medicine, Chosun University, Korea. 05 2006 31 05 2006 30 3 161 169 06 02 2006 25 05 2006 Copyright © 2006 Korean Diabetes Association 2006 Background

Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARγ-coactivator 1 (PGC-1) and Peroxisome proliferator-activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

 Methods

Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay.

 Results

The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARγ mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARα and PPARβ mRNA expressions in liver of OLETF and LETO rats were not observed.

 Conclusion

The liver PPARγ and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARγ and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARγ and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.

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Effects of caloric restriction on the body weight of LETO and OLETF rats.

Data are means ± SEM.

*: P < 0.01.

mRNA levels of PGC-1 in whole liver homogenates from Caloric-restricted LETO and OLETF rats (FD). Data are the ratio of the target mRNA to PGC-1 mRNA. The top portion of each figure is a gel representative of n = 3/group.

Data are means ± SEM.

*: P < 0.01.

mRNA levels of PPARα in whole liver homogenates from Caloric-restricted LETO and OLETF rats (FD). Data are the ratio of the target mRNA to PPARα mRNA. The top portion of each figure is a gel representative of n = 3/group.

Data are means ± SEM.

*: P < 0.05.

mRNA levels of PPARβ in whole liver homogenates from Caloric-restricted LETO and OLETF rats (FD). Data are the ratio of the target mRNA to PPARβ mRNA. The top portion of each figure is a gel representative of n = 3/group.

Data are means ± SEM.

*: P < 0.05.

mRNA levels of PPARγ in whole liver homogenates from Caloric-restricted LETO and OLETF rats (FD). Data are the ratio of the target mRNA to PPARγ mRNA. The top portion of each figure is a gel representative of n = 3/group.

Data are means ± SEM.

*: P < 0.05.

Primer Set

Blood Glucose Levels of Caloric-restricted LETO and OLETF Rats

Data are means ± SE, n = 5.

*: P < 0.05 vs. LETO group.

†: P < 0.01 vs. LETO group.