ω-3脂肪酸对哺乳期过度喂养大鼠胃组织脑肠肽生长激素释放肽及血清瘦素的影响

Effect of omega-3 polyunsaturated fatty acids diets after early over-feeding on expressions of ghrelin in gastric tissue and leptin in serum in adult rats

目的观察哺乳期过度喂养大鼠断乳后给予ω-3脂肪酸，其胃组织中脑肠肽生长激素释放肽（ghrelin）表达和循环中瘦素（1eptin）浓度的变化，探讨哺乳期过度喂养及断乳后不同饮食干预对成年期代谢综合征的影响及调控作用。方法雄性SD大鼠出生后分为正常喂养组（NF组，每窝10只）和过度喂养组（OF组，每窝3只），出生3周后断乳，OF组分别给予正常饮食（OF＋Con）、高脂饮食（OF＋HF）及ω-3不饱和脂肪酸饮食ω-3PUFAs，OF＋ω-3），NF组给予正常饮食（NF＋Con）和高脂饮食（NF＋HF）。每周记录体重及摄食量。6和16周时，进行糖耐量试验；酶联免疫吸附法分别测定各组血清leptin、ghrelin及甘油三酯（TG）浓度，实时定量PCR及免疫组织化学法分别测定各组胃组织ghrelinmRNA和蛋白表达浓度。结果16周时，OF＋HF组大鼠能量摄入、体重明显高于NF＋HF组（t=-3．453，P=0．014；t=-6．406，P=0．000），血清TG高于OF＋Con组（t=4．72，P=0．005），30min血糖浓度明显高于其他各组（F=16．249，P=0．000），血清leptin持续高于其他各组，胃组织ghrelinmRNA亦明显高于OF＋Con组（t=8．486，P=0．000），但胃组织ghrelin阳性细胞面积及血清ghrelin差异无统计学意义。16周时OF＋Con组血清leptin水平高于NF＋Con组（t=-3．274，P=0．031），OF＋HF组血清leptin水平高于OF＋Con组（t=3．028，P=0．014）。OF＋ω-3组上述指标与正常饮食组相比差异无统计学意义。结论哺乳期过度喂养对高脂饮食诱导的肥胖和糖脂代谢紊乱更加敏感，更易发生肥胖、糖脂代谢失调，血清leptin和胃组织ghrelinmRNA表达持续增加，加重leptin抵抗和摄食调控的紊乱。ω-3PUFAs能改善哺乳期过度喂养造成的脂肪组织过度积聚、糖耐量受损、leptin抵抗，维持正常的leptin和ghrelin浓度。

Objective To observe ghrelin expression in gastric tissue and serum leptin level of the early over-fed rats given ω-3 polyunsaturated fatty acids （PUFAs） diets after weaning, and explore the effects of early over-feeding and diets intervention on the metabolic syndrome in adult rats. Methods Male Sprague- Dawley rats were divided into normal feeding group （NF group, 10 per litter） or over-feeding group （OF group, 3 per litter） in postnatal day 3, and then different diets were given after weaning （postnatal day 21 ）.The OF group was separately given conventional diet （ OF ＋ Con group）, high-fat diet （ OF ＋ HF group）, or ω-3 PUFAs （ OF ＋ ω-3 group） ; while the NF group was separated into NF ＋ Con group and NF ＋ HF group. Body weight and food intake were recorded every week. In week 6 and week 16, glucose tolerance test was per- forfmed. Serum leptin, ghrelin, and triglyceride were assayed by enzyme-linked immuno-absorbent assay. Gh- relin mRNA and protein levels in gastric tissue were quantified by real-time PCR and immunohistochemistry. Results At week 16, energy intake, body weight and glucose intolerance in OF ＋ HF group were significantly higher than in NF ＋ HF group （t = - 3.453, P = 0. 014 ; t = - 6. 406, P = O. 000 ; F = 16. 249, P = 0. 000）, and serum triglycerides, ghrelin mRNA of gastric tissue were significantly higher than those of OF ＋ Con group （t = 4. 72, P = O. 005 ; t = 8. 486, P = O. 000）. At week 16, the serum leptin level in OF ω- Con group was higher than that in NF ＋ Con group （ t = - 3. 274, P = O. 031 ）, also higher in OF ＋ HF group than that in OF ＋ Con group （t =3.028, P =0. 014）. There were no significant differences in serum ghrelin and the area of ghrelin immuno-positive ceils in the gastric tissue among groups. The above indicators in OF ＋ ω-3 group were not different from those of NF ＋ Con group. Conclusions Over-feeding during the lactation period may lead to high susceptibility to obesity and disordered glucose and lipid metabolism. It can also increase serum leptin and ghrelin mRNA expression in gastric tissue, aggravate leptin resistance and feeding control disorders. Dietary ω-3 PUFAs offered protection against excessive accumulation of adipose tissue, glucose intolerance, leptin resistance, and maintained normal levels of leptin and ghrelin.