灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪脂質代謝之影響

第六章討論

6.8 灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪脂質代謝之影響

FAS能催化脂肪酸合成反應，屬於長期調控脂肪酸合成的限速酵素。研究指出單醣類對FAS的調控，較複合糖類更具顯著影響 (Semenkovich, 1997)。本篇研究結果顯示，HF組腎周脂肪內FAS蛋白表現量相較於Normal組，有稍微提高但沒有顯著差異，給予沒食子酸30 mg/kg B.W.濃度下，相較於高果糖組明顯增加FAS

57 蛋白表現量，且達顯著差異。

b.脂肪細胞三酸甘油酯脂解酶(Adipose triglyceride lipase; ATGL)

游離脂肪酸主要由脂解酶分解三酸甘油酯而來，脂解功能異常將導致能量代謝異常，引起肥胖及胰島素阻抗(Zimmermann et al., 2004)。體內主要分解 TG 的脂解酶包括 HSL 與 ATGL。本篇研究顯示實驗動物灌食沒食子酸 6 週後，HF 組 ATGL 顯著低於 Normal 組，顯示高果糖誘導模式將會降低脂解作用。GA30 組顯著高於 HF 組，但與 GA10 組沒有顯著差異，由此可知灌食沒食子酸 30 mg/kg B.W.

可顯著提升 ATGL 增加脂解作用，但灌食沒食子酸 10 mg/kg B.W.則沒有影響。

58 第七章結論

本篇研究結果可歸納以下幾點結論：

1.灌食 30 mg/kg B.W.沒食子酸可有效改善高果糖飼料誘導高血糖 Wistar 大鼠高血糖、高胰島素血症等現象。

2.灌食 30 mg/kg B.W.沒食子酸可有效降低高果糖飼料誘導高血糖 Wistar 大鼠體脂肪及血漿中三酸甘油脂濃度。

3.灌食 30 mg/kg B.W.沒食子酸可藉由提高 Glut4、IR、PKC-ζ等胰島素訊息傳遞蛋白，來改善高果糖飼料誘導高血糖 Wistar 大鼠葡萄糖代謝。

4.灌食 30 mg/kg B.W.沒食子酸可藉由提高 ATGL 蛋白表現量，來增加高果糖飼料誘導高血糖 Wistar 大鼠三酸甘油酯分解，並降低體脂肪。

Normal HF HF+PIO30 HF+GA30 HF+GA10

Plasma insulin (mg/dl)

Figure.5-1 Oral glucose tolerance test (OGTT) curve on plasma glucose level of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

＊: Indicates a signify difference (p<0.05) compared with the other group.

Values were calculated as mean±S.E for six rats in each group.

＊

＊＊

＊

Normal HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasm glucose(mg/dL)

0 50 100 150 200 250

圖 5-2 灌食沒食子酸 4 週後大鼠於禁食情況下血漿中葡萄糖濃度之變化。

Figure.5-2 Plasma glucose levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~b Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

b b

Normal HF HF+pio(30) HF+GA(30) HF+GA(10)

Fructosamine (umol/L)

0 20 40 60 80 100 120 140

圖 5-3 灌食沒食子酸 4 週後大鼠於禁食情況下血漿中果糖胺濃度之變化。

Figure.5-3 Plasma fructosamine levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

a

bc bc bc

Normal HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasma insulin mg/dL

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

圖 5-4 灌食沒食子酸 4 週後大鼠於禁食情況下血漿中胰島素濃度之變化。

Figure.5-4 Plasma insulin levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

Values were calculated as mean±S.E for six rats in each group.

b b

NORMAL HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasma C-peptide(pmol/L)

0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16

圖 5-5 灌食沒食子酸 4 週後大鼠於禁食情況下血漿中

C 胜鏈濃度之變化。

Figure.5-5 Plasma C-peptide levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

a

Normal HF HF+Pio(30) HF+GA(30) HF+GA(10)

Adipose tissue (g)

0 2 4 6 8 10 12 14

圖 5-6 灌食沒食子酸 4 週後大鼠體內脂肪組織堆積之變化。

Figure.5-6 Adipose tissue accumulation of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

Values were calculated as mean±S.E for six rats in each group.

Normal HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasma triglyceride (mg/dL)

Figure.5-7 Plasma triglyceride levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ) Values were calculated as mean±S.E for six rats in each group.

a

CTR HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasma free fatty acid (mmol/L)

0.0

Figure.5-8 Plasma free fatty acid levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ) Values were calculated as mean±S.E for six rats in each group.

a

^ab

Normal HF HF+Pio(30) HF+GA(30) HF+GA(10)

Plasma HDL-C (mg/dL)

0 20 40 60 80

圖 5-9 灌食沒食子酸 4 週後大鼠於禁食情況下血漿中高密度脂蛋白濃度之變化。

Figure.5-9 Plasma high density lipoprotein levels of rats after 4 weeks feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

Values were calculated as mean±S.E for six rats in each group.

ab a

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Glucose transporter 4 relative expression

0.0

Figure.5-10 Relative expression of glucose transporter 4 in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

ab a

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10)

Insulin receptor relative expression

0.00

Figure.5-11 Relative expression of insulin receptor in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

b a

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Protein kinase C -zeta relative expression

0 10 20 30 40

PKC-ζ(68KDa) α-tublin(55KDa)

圖 5-12 灌食沒食子酸 4 週後對大鼠腎周脂肪 PKC-ζ蛋白表現量之影響。

Figure.5-12 Relative expression of protein kinasein C-zeta in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Phosphofructokinase relative expression

Figure.5-13 Relative expression of phosphofructokinase in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Pyruvate kinase relative expression

Pyruvate kinase(62KDa)

α-tublin(55KDa)

圖 5-14 灌食沒食子酸 4 週後對大鼠腎周脂肪 PK 蛋白表現量之影響。

Figure.5-14 Relative expression of pyruvate kinase in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

Values were calculated as mean±S.E for six rats in each group.

b b

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Fatty acid synthase relative expression

0 1 2 3 4 5

FAS(273KDa)

α-tublin(55KDa)

圖 5-15 灌食沒食子酸 4 週後對大鼠腎周脂肪 FAS 蛋白表現量之影響。

Figure.5-15 Relative expression of fatty acid synthase in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~c Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

b a

Normal HF HF+PIO(30) HF+GA(30) HF+GA(10) Adipose triglyceride lipase relative expression

0.0

Figure.5-16 Relative expression of adipose triglyceride lipase in perirenal fat isolated from rats after 4 week feeding test.

Normal:Normal rats treated with saline HF: High fructose diet rats treated with saline

HF+Pio(30):High fructose diet rats treated with pioglitazone(30 mg/kg B.W.) HF+GA(30):High fuctose rdiet rats treated with gallic acid(30 mg/kg B.W.) HF+GA(10):High fructose diet rats treated with gallic acid(10 mg/kg B.W.) a~d Letter is significantly different among all samples tested( P< 0.05 ).

Values were calculated as mean±S.E for six rats in each group.

c a

圖 7-1、沒食子酸於脂肪細胞中調控醣類與脂質代謝之可能機制

Figure. 7-1 The postulated mechanism for gallic acid to regulate carbohydrate and lipid metabolism of adipocytes in high fructose diet-induced diabetic rats.

Glucose

Fat accumulation ↓

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在文檔中沒食子酸(gallic acid)對高果糖飼料誘導高血糖大鼠血糖及脂質代謝之影響 (頁 56-0)

第六章 討論

6.8 灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪脂質代謝之影響

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C 胜鏈濃度之變化。

a

a

a

Fat accumulation ↓

第六章討論