11β HSD-1 and PAI-1 gene expression fructose induced metabolic syndrome rats

T.C. ISTANBUL BILIM

UNIVERSITY

Backround:

Metabolic syndrome (MetS) is an important health issue worldwide. It is a prevalent and complex disease, characterized by the variable

coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to

innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by

the lack of realistic models. In recent years, high comsumption of fructose has been shown to be an important factor of MetS. And, the presence and the

increased level of expressions of 11β HSD-1 and PAI-1 genes in MetS were also shown to play an important role in the pathogenesis of MetS.

Aim:

The aim of this study was to investigate the effect of 20% fructose in the development of MetS in rats by the use of the biochemical and genetics

approaches.

Material and Metods:

The study group was composed of MetS groups (n=10 rats) who were fed with water containing 20% fructose and control groups

(n=10 rats) who were fed with only water for 15 weeks. Serum levels of glucose, insulin, total cholesterol, LDL, HDL, VLDL, ALT, AST, CRP and cortisol were

measured. The gene expression levels of 11β HSD-1 and PAI-1 from liver and omental adipose tissues were also investigated by QRT-PCR.

RESULTS

Conclusion:

These findings show that there are statistically significant differences in the biochemical parameters as well as the gene expression levels of 11β

HSD-1 and PAI-1 genes in MetS group and these changes prove the contributory role of the 20% fructose consumption to the development of MetS.

(Mean±SE) Control (n=10) MetS (n=10) P Value Weight (gr) 355±1.92 394.1±5.03

_0.000

Skin Thickness (cm²) 0.57±0.01 1.47±0.04

0.000

Waist Circumference (cm) 17.3±0.15 23.5±0.34

_0.000

ALT (U/L) 84.9±7.35 140.7±71.66 0.280 AST (U/L) 105.4±1.82 241.1±96.72

0.003

Glucose (mg/dL) 286.9±11.07 467.8±22.63

_0.000

Insulin (ng/ml) 2.76±0.4 3.69±0.72 0.813 HOMA-IR 45.85±7.38 107.3±23.9

0.010

Total Cholesterol (mg/dL) 98.2±2.43 134.8±7.14

_0.000

CRP (mg/dL) 0.006±0.001 0.03±0.005

_0.000

Triglycerides (mg/dL) 86.9±6.32 176.9±2.63

_0.000

HDL (mg/dL) 79.7±2.08 45.8 ±1.89

_0.000

LDL (mg/dL) 7.06±0.73 16.26±2.13

_0.000

VLDL (mg/dL) 15.9±093 30.8±1.32

_0.000

Cortisol (µg/dL) 5.31±051 7.24±0.43

_0.015

(Mean±SE) Control (n=10) MetS (n=10) P Value Initial Weight (gr) 257±2.13 256±3.63 N.S

Initial Skin Thickness (cm²) 0.43±0.01 0.44±0.01 N.S

Initial Waist Circumference (cm) 14.6±0.16 14.5±0.16 N.S

ALT (U/L) 38.2±2.87 37±3.43 N.S AST (U/L) 58.8±1.63 56±5.84 N.S Glucose (mg/dL) 92.7±3.15 92.8±6.35 N.S Insulin (ng/ml) 3.86±0.56 3.83±1.04 N.S HOMA-IR 21.88±3.40 19.55±4.86 N.S Total Cholesterol (mg/dL) 80.5±2.54 81.8±4.74 N.S Triglycerides (mg/dL) 35.3±1.25 37.7±5.29 N.S HDL (mg/dL) 74.7±1.46 79.3±2.62 N.S LDL (mg/dL) 5.08±0.61 5.54±0.88 N.S VLDL (mg/dL) 5.5±0.37 5.9±0.69 N.S Cortisol (µg/dL) 2.6±0.09 2.59±0.1 N.S

The data are expressed as mean values plus or minus the standard deviatiation unless otherwise stated. Weight, skin thickness, waist circumference, glucose, total cholesterol, CRP, triglycerides, HDL, LDL and VLDL were significantly increased in the rats in MetS group compared with those in the control group(p<0.001). AST, HOMA-IR, cortisol were higher in MetS group compared to control group(p<0.05).

The data are expressed as mean values plus or minus the standard deviatiation unless otherwise stated. Weight, skin thickness, waist circumference, glucose, total cholesterol, CRP, triglycerides, HDL, LDL, VLDL, AST, HOMA-IR and cortisol were no difference between the groups (p>0.05).

Table1: Anthropometric and biochemical parameters of the study group before starting the fructose diet. Table2: Anthropometric and biochemical parameters in the study group at the end of 15-week-fructose diet.

Figure 1: Weight measurement of MetS and the control (cont) groups during 15 weeks Figure 2: Waist circumference measurement of MetS and the control (cont) groups during 15 weeks Figure 3: Skin thickness measurements of MetS and the control (cont) groups during 15 weeks

Figure 4: Fat accumulation of the study groups after the 15 week period. A; no fat accumulation was observed in control group, B; MetS group rats the accumulation of fatty (*fat accumulation was observed in MetS group).

Figure 5: 11β HSD-1 and PAI-1 mRNA expression level of MetS and control group rats in omental adipose tissue and liver tissue. 11β HSD-1 and PAI-1 mRNA expression in liver tissue were significantly higher in MetS group rats compared to control group rats. Furthermore PAI-1 mRNA expression in omental adipose tissue were significantly higher in MetS group rats compared to control group rats (* p<0.05).

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11β HSD-1 AND PAI-1 GENE EXPRESSIONS IN FRUCTOSE INDUCED METABOLIC SYNDROME RATS

Gokce Akan

1

_{, Oznur Inan}

2

_{, Fatmahan Atalar}

3

_{, Uzay Gormus}

4

_{, Ayhan Bilir}

5

_{, Kursat Ozdilli}

6

_{, Cavlan Ciftci}

7

_{and Tuncay Altug}

1

1

_{Department of Medical Biology and Genetics, Istanbul Bilim University, Istanbul, Turkey}

2

_{Department of Experimental Animals Laboratory, Research Center, Bezmialem Foundation University, Istanbul, Turkey}

3

_{Department of Growth-Development and Pediatric Endocrinology, Child Health Institute, Istanbul University, Istanbul, Turkey}

4

_{Department of Medical Biochemistry, Istanbul Bilim University, Faculty of Medicine, Istanbul, Turkey}

5

_{Department of Histology and Embryology Istanbul Faculty of Medicine, Istanbul,Turkey}

6

_{Institu of Health, Halic University, Istanbul, Turkey}