EFFECTS OF HIGH FAT-FEEDING TO RATS ON THE INTERRELATIONSHIP OF BODY-WEIGHT, PLASMA-INSULIN, AND FATTY ACYL-COENZYME-A ESTERS IN LIVER AND SKELETAL-MUSCLE
EFFECTS OF HIGH FAT-FEEDING TO RATS ON THE INTERRELATIONSHIP OF BODY-WEIGHT, PLASMA-INSULIN, AND FATTY ACYL-COENZYME-A ESTERS IN LIVER AND SKELETAL-MUSCLE
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DOI：
10.1016/0026-0495(92)90221-u
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发表时间：
1992-05-01
影响因子：
9.8
通讯作者：
SHRAGO, E
中科院分区：
文献类型：
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作者：
CHEN, MT;KAUFMAN, LN;SHRAGO, E
与两种不同的高碳水化合物饮食的动物相比，喂食高饱和脂肪饮食的大鼠消耗了更多的能量，增加了更多的体重，并表现出高胰岛素血症(P<；0.05)，而空腹血糖水平没有上升。饲喂高脂饲料的大鼠肝脏和骨骼肌中的总脂肪酰基辅酶A(CoA)浓度分别比其他饲料组高18%(P<；0.0001)和46%(P<；0.0001)。高脂饮食大鼠两种组织中主要的长链脂肪酰辅酶A分子种类反映了饮食中的脂肪酸组成。油酰辅酶A、棕榈酰辅酶A和硬脂酰辅酶A分别占肝脏和骨骼肌脂肪酰辅酶A总量的29%、21%和16%。高脂饲料组大鼠肝脏和骨骼肌中这三种脂肪酰辅酶A酯的含量显著高于其他饲料处理组(P<；.0001)。相比之下，高脂饲养后两种组织中亚油酰辅酶A的浓度都较低(P<；.0001)。在喂食高脂饮食的大鼠中，血浆胰岛素水平与体重增加或体重增加显著相关(胰岛素和体重增加的r=.80，P<；.001；胰岛素和体重的r=.73，P<；.001)。高脂喂养大鼠肝脏和骨骼肌中总脂肪酰辅酶A酯含量与血浆胰岛素浓度也有很强的相关性(肝脏r=0.80，P<0.01；骨骼肌r=0.78，P<0.01)。无论采取何种饮食治疗，组织脂肪酰辅酶A水平与体重或体重增加均呈正相关(肝脏总酰辅酶A与体重或体重增加呈正相关(r=0.75，P<0.05)；肌肉脂肪酰辅酶A含量与体重呈正相关(r=0.73，P<0.01)；肌肉总酰基辅酶A与体重呈正相关(r=0.77，P<0.01)。这些结果清楚地表明，通过将饮食中以碳水化合物为主的大量营养素比例改变为以脂肪为主的饮食比例而导致的饮食肥胖导致组织脂肪酰辅酶A水平显著增加，这表明与高脂肪摄入相关的脂肪酸的利用更多。通过底物竞争抑制葡萄糖代谢，称为葡萄糖-脂肪酸循环，导致胰岛素抵抗的发生。组织脂肪酰辅酶A组成可作为胰岛素抵抗和高胰岛素血症发展的指标或原因因素。
Rats fed a high-saturated fat diet consumed more energy, gained more weight, and displayed hyperinsulinemia (P< .05) without an elevation in the fasting plasma glucose level, compared with animals on two different high-carbohydrate diets. The total fatty acyl-coenzyme A (CoA) concentration was 18% (P< .0001) and 46% (P< .0001) higher in liver and skeletal muscle, respectively, from rats fed the high-fat diet compared with each of the other diet groups. Major long-chain fatty acyl-CoA molecular species of both tissues in high fat-fed rats reflected the fatty acid profile of the diet. Approximately 29%, 21%, and 16% of total liver and skeletal muscle fatty acyl-CoAs were comprised of oleoyl-CoA, palmitoyl-CoA, and stearoyl-Coa, respectively. The amounts of these three fatty acyl-CoA esters were significantly higher in liver and skeletal muscle after high-fat feeding than with the other diet treatments (P< .0001). In contrast, the concentration of linoleoyl-CoA was lower in both tissues after high-fat feeding (P< .0001). In rats fed the high-fat diet, plasma insulin levels were significantly correlated with gain in body weight or body weight (r= .80,P< .001 for insulin and gain in body weight;r= .73,P< .001 for insulin and body weight). Total fatty acyl-CoA ester content in liver and skeletal muscle was also strongly correlated with the plasma insulin concentration in high fat-fed rats (r= .80,P< .001 for liver;r= .78,P< .001 for skeletal muscle). Regardless of diet treatments, a positive correlation between tissue fatty acyl-CoA level and gain in body weight or body weight was reported from all experimental rats (r= .75,P< .001 for hepatic total acyl-CoA and body weight or weight gain;r= .73,P< .001 for muscle acyl-CoA content and body weight;r= .77,P< .001 for muscle total acyl-CoA and weight gain). These results clearly demonstrate that the dietary obesity induced by altering the macronutrient proportion of the diet from predominantly carbohydrate to predominately fat causes a marked increase in tissue fatty acyl-CoA levels, suggesting the greater utilization of fatty acids associated with high-fat intake. The inhibition of glucose metabolism by substrate competition, termed the glucose-fatty acid cycle, leads to the development of insulin resistance. Tissue fatty acyl-CoA composition could serve as an indicator or could be a causal factor in the development of insulin resistance and hyperinsulinemia.