영양과 호르몬상태에 따른 Plasminogen Activator Inhibitor-1, Leptin 및 Resistin 유전자 발현조절에 관한 연구
Regulation of Plasminogen Activator Inhibitor-1, Leptin and Resistin Gene Expression by Nutritional and Hormonal Status
영양 호르몬 Plasminogen Activator Inhibitor-1 Leptin Resistin 유전자 발현조절;
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PAI-1 (plasminogen activator inhibitor-1), leptin, and resistin are synthesized and secreted by fat cells of rodents and have recently been postulated to be an important link to obesity. This study was performed to identify the regulation of PAI-1, leptin, and resistin gene expression according the nutritional and hormonal status. Male Sprague-Dawley rats were fed with control diet, 40% energy-restricted diet, high animal fat diet, or high plant fat diet for 8 weeks. The visceral and subcutaneous adipose tissues were dissected and the mRNA levels of PAI-1 were measured by semi-quantitative RT-PCR. In the epididymal fat tissue, the level of PAI-1 mRNA was the lowest in the energy-restricted animals, and was the highest in the animals fed with high fat diet. Also, in the peritoneal fat tissue, the level of PAI-1 mRNA was the lowest in the energy-restricted animals, and was the highest in the animals fed with high fat diet. However, in the subcutaneous fat tissue, the level of PAI-1 mRNA was the lowest in the energy-restricted animals, but was similar between in the animals fed with control diet and with high fat diet. These finding suggest that the nutritional regulation of gene expression encoding PAI-1 from adipocytes may vary according th the types of adipose tissue, and the visceral adipose tissue might be more sensitively involved in the nutritional regulation of PAI-1 gene expression compared to the subcutaneous fat tissue. The ob/ob mice were divided into four groups according to nutritional status: control, 48 hour fasting, 48 hour-fasting/12 hour-refeeding, and 48 hour-fasting/24 hour-refeeding. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. In visceral fat tissue, the level of PAI-1 mRNA increased markedly when 48h-fasted animals were refed a high carbohydrate-low fat diet. However, fasting/refeeding did not appreciably change PAI-1 mRNA levels in subcutaneous fat tissue. Similar results were obtained for resistin mRNA levels in both types of fat tissues. These findings suggest that visceral adipose tissue might be more sensitively tissue. The level of leptin mRNA decreased markedly in the 48h- fasted animals, and increased markedly when 48h-fasted animals were refed with a high carbohydrate-low fat diet. The nutritional regulation of leptin mRNA showed similar patterns in both types of fat tissues. In conclusion, the nutrition of gene expression encoding PAI-1, resistin, and leptin from adipocytes may vary according to the type of adipose tissue. The 3T3-L1 preadipocytes were grown in growth medium and differentiated in the medium by adding dexamethasone, 1-methyl-3-isobutylxanthine for 2 days, and then they were grown in the growth medium for 4-5 days to accumulate fat. The 3T3-L1 adipocytes were incubated for 72 hours in serum free medium with each concentration of insulin (0.5μM), dexamethasone (1μM), and triiodothyronine (0.05μM). PAI-1 gene expression was increased 1.2-fold by 0.5μM insulin. Also, resistin and leptin gene expression were dramatically upregulated by insulin. In the presence of 1μM dexamethasone, PAI-1 gene expression was decreased 2-fold but resistin and leptin gene expression were increased 1.2-, 8-fold. The level of PAI-1 mRNA was increased by insulin, dexamethasone, T3, dexamethasone plus T3, and insulin plus dexamethasone plus T3 approximately 2.6-, 3-, 2-, 2- and 1.6-fold, respectively. The level of resistin mRNA was increased by insulin, dexamethasone, T3, insulin plus dexamethasone, and insulin plus T3 approximately 2.7-, 2.5-, 2-, 2-, and 1,7-fold, respectively. Likewise, the level of leptin mRNA was increased mainly about 2 to 3-fold in treatment of hormone. Taken together, our results suggest that PAI-1, resistin and leptin gene expression is upregulated by insulin, dexamethasone and T3.