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m m H g

LF HF HF+SW SW

圖圖

圖 4 – 18 大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗飲食飲食飲食飲食 5 個月之收縮壓個月之收縮壓個月之收縮壓(個月之收縮壓(((Systolic))))、、舒張壓、、舒張壓舒張壓舒張壓((((Diastolic))))和脈搏和脈搏和脈搏和脈搏(((Pulse)( )))

Fig 4-18 Systolic, diastolic and pulse of rats fed experimental diets for 5 months.

Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

Systolic 0.2330 0.0004 0.4918

Diastolic 0.2248 0.0178 0.2662

Pulse 0.0155 0.0002 0.7895

第四章第四章 第四章第四章 結果結果結果結果

b

ab

ab a

0 0.1 0.2 0.3 0.4 0.5

mature / immature

LF HF HF+SW SW

圖圖

圖 4 – 19 以以以以 Western bolt 分析分析分析分析大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗飲食飲食飲食 5 個月之飲食 個月之個月之個月之肝臟肝臟肝臟肝臟 mature (68 kD)/ immature (128 kD) SREBP-1c 蛋白質表現量蛋白質表現量蛋白質表現量 蛋白質表現量

Fig 4-19 Western blot analysis of immature ( membrane ; 128 kDa) and mature (nuclear; 68 kDa) SREBP-1c protein in liver of rats fed experimental diets for 5 months. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

SREBP-1c 0.5524 0.0181 0.1188

第四章第四章 第四章第四章 結果結果結果結果

b

ab

a

a

0 0.1 0.2 0.3 0.4 0.5 0.6

nuclear / cytosol

LF HF HF+SW SW

圖 圖 圖

圖 4 – 20 以以 Western bolt 定量分析大鼠餵食試驗以 定量分析大鼠餵食試驗定量分析大鼠餵食試驗定量分析大鼠餵食試驗飲食飲食飲食 5 個月之肝臟飲食 個月之肝臟個月之肝臟 nuclear / cytosol 個月之肝臟 ChREBP 蛋白質表現量蛋白質表現量蛋白質表現量蛋白質表現量

Fig 4-20 Western blot analysis of nuclear and cytosol ChREBP protein in liver of rats fed experimental diets for 5 months. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

ChREBP 0.4183 0.0249 0.2263

第四章第四章 第四章第四章 結果結果結果結果

c

b b

a

0 50 100 150 200

Diameter (μm )

LF HF HF+SW SW

圖圖

圖 4 – 21 大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗大鼠餵食試驗飲食飲食飲食飲食 5 個月之腹膜後脂肪組織切片與個月之腹膜後脂肪組織切片與個月之腹膜後脂肪組織切片與脂肪細胞個月之腹膜後脂肪組織切片與脂肪細胞脂肪細胞脂肪細胞平均直徑平均直徑平均直徑 平均直徑

Fig 4-21 Average diameter of adipocyte in retroperitoneal fat of rats fed experimental diets for 5 months. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

RE diameter <<<<0.0001 <<<<0.0001 <<<<0.0001

第四章第四章 第四章第四章 結果結果結果結果 表表

表 4 - 6 大鼠餵食試驗飲食大鼠餵食試驗飲食大鼠餵食試驗飲食大鼠餵食試驗飲食 5 個月之個月之個月之肝臟和脂肪組織內基因表現量個月之肝臟和脂肪組織內基因表現量肝臟和脂肪組織內基因表現量肝臟和脂肪組織內基因表現量1,2,3

Table 4-6 The gene expression levels of rats fed experimental diets for 5 months. 1,2,3

1mRNA levels of target genes were normalized to 36B4.. The mRNA level is expressed as a fraction of that in the LF group assigned a value of 1

2Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05. The significance of differences between the induced group and shift group (HF vs, HF/C; HF+SW vs. HF+SW/C; SW vs.

SW/C) respectively was analyzed statistically by Student’s t tests, *P < 0.05.

3FAS::::fatty acid synthase;;ACC:; :::acetyl-CoA carboxylase;;;;GK::glucokinase;: ;;;TNF-α::::tumor necrosis factor-α;;;;PAI-1::::plasminogen activated inhibitor-1;;;; Mest::::mesoderm specific transcript.

p value from Two-way ANOVA Treatment

Group LF HF HF / C HF+SW HF+SW /

C SW SW / C

fat sugar fat ×

sugar liver

FAS 1.04±0.35 1.52±0.81 0.57±0.27 1.05±0.03 0.60±0.31 2.27±1.00 0.36±0.21* 0.5707 0.7948 0.5392

ACC 1.03±0.31 1.50±0.65 1.04±0.44 1.26±0.19 1.02±0.43 1.60±0.77 1.01±0.56 0.7046 0.7012 0.2188

GK 1.00±0.10 b 0.84±0.18 b 6.81±0.35* 2.43±1.22 a 6.35±1.19 1.03±0.32 b 3.91±0.10* 0.2176 0.0562 0.0647

adipose tissue

Adiponectin 1.04±0.23 0.90±0.20 1.94±0.81 0.59±0.32 0.82±0.5 0.91±0.12 1±0.66 0.1764 0.1464 0.5122 TNF-α 1.03±0.27 b 3.71±2.07 a 0.91±0.08* 4.20±5.11 ab 2.09±0.61 1.09±0.38 b 0.40±0.25 0.0078 0.7538 0.623 Resistin 1.06±0.38 b 4.54±0.81 a 3.05±0.29* 3.25±3.34 a 1.36±1.29 0.88±0.11 b 0.58±0.16 0.0001 0.1453 0.2897 PAI-1 1.03±0.25 c 7.84±1.34 a 0.75±0.52* 2.23±1.07 bc 1.87±0.76 2.87±1.21 b 1.44±0.80 0.0306 0.4569 0.0003 Leptin 1.11±0.55 b 3.15±0.45 a 0.37±0.20* 2.22±0.07 ab 2.05±0.56 2.96±1.61 ab 1.08±1.01 0.0430 0.4131 0.0312 Mest 1.07±0.39 a 0.69±0.34 ab 0.75±0.52 0.49±0.23 b 1.87±0.76* 0.52±0.26 b 1.44±0.80* 0.1419 0.0110 0.1859

第四章第四章 第四章第四章 結果結果結果結果 表表

表 4 - 7 四組小鼠之攝食四組小鼠之攝食四組小鼠之攝食四組小鼠之攝食、、、飲水和能量攝取、飲水和能量攝取飲水和能量攝取飲水和能量攝取1

Table 4-5 Food, water and calory intake of mice in four groups.1

Treatment Group LF HF HF+SW SW

number 15 15 15 15

Food intake (g/d) 3.3 2.1 1.03 1.9 Water intake (mL/d) 4.28 4.31 11.5 10.91 Total Calory intake (Kcal/d) 11.22 10.54 18.98 19.55

1 Calory content for chow diet: 3.4 kcal/g; for high fat diet: 5 kcal/g; for sucrose-containing drinking water : 1.2 kcal/mL.

第四章第四章 第四章第四章 結果結果結果結果 表表

表 4 - 8 小鼠餵食試驗飲食小鼠餵食試驗飲食小鼠餵食試驗飲食小鼠餵食試驗飲食 5 個月之初個月之初個月之初、個月之初、、、終體重及體重增加量終體重及體重增加量終體重及體重增加量終體重及體重增加量4

Table 4-8 The initial and final body weight and body weight gain of mice fed experimental diets for 5 monthes

1Initial body weight : at 0 month (n=15 for LF, HF,HF+SW and SW)

2 Final body weight : at 5 month (n=15 for LF, HF+SW ; n=7 for HF,SW)

3Body weight gain : ( final body weight-initial body weight) / 150d. Values are means ± SD.

4P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups.

The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

Treatment Group LF HF HF+SW SW

fat sugar fat × sugar

1Initial body weight (g) 20.5±0.67 b 22.53±1.02 a 22.5±1.05 a 22.5±0.99 a

2Final body weight (g) 26.16±1.24 c 36.98±1.87 a 37.42±4.63 a 32.39±3 b <0.0001 0.0022 0.0071

3Body weight gain (g / d) 0.03±0.01 c 0.09±0.01 a 0.10±0.03 a 0.06±0.02 b <0.0001 0.0151 0.0294

第四章第四章 第四章第四章 結果結果結果結果 表表

表 4 - 9 小鼠餵食試驗飲食小鼠餵食試驗飲食小鼠餵食試驗飲食小鼠餵食試驗飲食 5 個月之絕對與相對組織重個月之絕對與相對組織重個月之絕對與相對組織重個月之絕對與相對組織重1

Table 4-9 The absolute and relative tissue weights of mice fed experimental diets for 5 months.

1Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

Treatment Group LF HF HF+SW SW

fat sugar fat × sugar Liver

liver (g) 1.14±0.13 c 1.40±0.22 b 1.84±0.50a 1.39±0.13 a <0.0001 0.0007 0.6619

liver weight/final body weight×100% 4.8±0.49 a 3.99±0.45b 5.02±0.52 a 4.58±0.26 a 0.4017 0.0110 0.0010 Adipose tissue

第四章第四章 第四章第四章 結果結果結果結果

c

a

a

b

0 2000 4000 6000 8000 10000

se ru m L ep ti n ( n g / m L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 22 小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第 5 個月時禁食血清個月時禁食血清個月時禁食血清 Leptin 個月時禁食血清

Fig 4-22 The fasting serum leptin levels of mice fed experimental diets for 5 months.

Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

5 month <0.0001 0.0021 0.0010

第四章第四章 第四章第四章 結果結果結果結果

5000 10000 15000

Serum Adiponectin ( ng / mL)

LF HF HF+SW SW

圖圖

圖 4 – 23 小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第 5 個月時禁食禁食血清個月時禁食禁食血清個月時禁食禁食血清個月時禁食禁食血清 Adiponectin

Fig 4-23 The fasting serum adiponectin levels of mice fed experimental diets for 5 months. Values aremeans ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups (LF, HF, HF +SW and SW) was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

5 month 0.1441 0.5667 0.4086

第四章第四章 第四章第四章 結果結果結果結果

c c ab d

ab b a

ab

b c c

a

a

b a

b

0 0.5 1 1.5 2 2.5

0 1 2 5

month

S er um T ri gl y ce ri d e ( m m o l / L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 24 小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第 0、、、、1、、2 和、 和和和 5 個月時禁食血清個月時禁食血清個月時禁食血清個月時禁食血清 Triglyceride((((TG)

Fig 4-24 The fasting serum triglyceride levels of mice fed experimental diets for 0, 1, 2 and 5 months. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p <

0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

1 month 0.0023 <0.0001 <0.0001 2 month 0.0009 <0.0001 <0.0001

5 month 0.0572 0.0116 <0.0001

第四章第四章 第四章第四章 結果結果結果結果

c d b c

b a

a ab

a a a

a c

b a b

0 1 2 3 4 5 6 7

0 1 2 5

month

Se ru m C h o le st er o l ( m m o l / L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 25 小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第 0、、1、、 、、、2 和和 5 個月時禁食血和 個月時禁食血個月時禁食血 Cholesterol(個月時禁食血 (((TC)))

Fig 4-25 The fasting serum cholesterol levels of mice fed experimental diets for 0, 1, 2 and 5 months. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p <

0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

1 month <0.0001 <0.0001 <0.0001

2 month <0.0001 0.0817 0.0010

5 month <0.0001 <0.0001 0.3793

第四章第四章 第四章第四章 結果結果結果結果

表表

表 4 - 10 小鼠餵食試驗飲食小鼠餵食試驗飲食小鼠餵食試驗飲食 5 個月之小鼠餵食試驗飲食 個月之個月之個月之肝臟肝臟肝臟肝臟、、、肌肉內脂質含量、肌肉內脂質含量肌肉內脂質含量肌肉內脂質含量1

Table 4- 8 The absolute and relative liver and muscle lipid concentrations of mice fed experimental diets for 5 months.

1Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests.

Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

第四章第四章 第四章第四章 結果結果結果結果

b b

a

a b

b b

b

0 2 4 6 8 10 12 14

0 1 2 5

month

Blood Glucose ( mmol / L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 26 小鼠餵食試驗第小鼠餵食試驗第小鼠餵食試驗第小鼠餵食試驗第 0、、1、、 、、、2 和和 5 個月時禁食血清葡萄糖和 個月時禁食血清葡萄糖個月時禁食血清葡萄糖 個月時禁食血清葡萄糖

Fig 4-26 The fasting blood glucose levels of mice fed experimental diets for 0, 1, 2 months. The fasting serum glucose levels of mice fed experimental diets for 5 month.

Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p <

0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

1 month 0.0004 0.0062 0.0077

2 month 0.2423 0.8674 0.6019

5 month 0.0014 0.0032 0.0451

第四章第四章 第四章第四章 結果結果結果結果

c

ab a

bc

0.00 0.20 0.40 0.60 0.80 1.00 1.20

se ru m I n su li n ( n g / m L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 27 小鼠餵食試驗第小鼠餵食試驗第小鼠餵食試驗第小鼠餵食試驗第 5 個月時禁食血清胰島素個月時禁食血清胰島素個月時禁食血清胰島素個月時禁食血清胰島素

Fig 4-27 Fasting serum insulin levels of mice fed experimental diets for 5 month. Values are means ± SD. P-values for fat, sugar and their interaction were analyzed by two-way ANOVA among LF, HF, HF+SW and SW groups. The significance of differences among the four groups was analyzed statistically by Duncan’s multiple range tests. Values not sharing the same superscript letter are significantly different, p < 0.05.

p values from Two-way ANOVA

fat sugar fat × sugar

5 month 0.0030 0.5697 0.8894

第四章第四章 第四章第四章 結果結果結果結果

b b b b

b

a a a a

a

b b b b

b c

b b b

b

0 2 4 6 8 10 12 14 16 18

0 30 60 90 120

min

Serum Glucose ( mmol / L )

LF HF HF+SW SW

圖 圖 圖

圖 4 – 28 小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第小鼠餵食試驗飲食第 5 個月時葡萄糖耐量試驗個月時葡萄糖耐量試驗個月時葡萄糖耐量試驗個月時葡萄糖耐量試驗

Fig 4-28 Oral glucose tolerance tests (OGTT) performed on mice fed experimental diets for 5 months. A glucose load was given and then, at the indicated time points,

Fig 4-28 Oral glucose tolerance tests (OGTT) performed on mice fed experimental diets for 5 months. A glucose load was given and then, at the indicated time points,

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