Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression
Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression
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DOI：
10.1111/j.1463-1326.2004.00312.x
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Storlien, L
中科院分区：
文献类型：
--
作者：
Huang, XF;Xin, X;Storlien, L
目的：饮食中的脂肪酸分布与脂肪的卡路里百分比无关，是身体肥胖的主要调节因素。本研究探讨了膳食脂肪含量和类型对慢性膳食诱导肥胖小鼠模型的脂肪储存和下丘脑基因表达的影响。方法：饮食干预包括两个方面：(1)与低脂饮食(LF)相比，13周肥胖饮食诱导肥胖；(2)用高n-3多不饱和脂肪(PUFA)和低脂饮食(LF)检测肥胖的可逆性。54只C57BL/6小鼠饲喂高脂(59千卡)饲料13周后，按体重增长上下限分为饮食诱导性肥胖(DIO)和饮食抵抗(DR)小鼠。然后将DIO小鼠细分为三组，进行为期6周的二级饮食干预。其中两组被切换到高n-3PUFA(DIO-N3)或低脂(Kcal，DIO-LF中10%)饮食，而第三组(对照组)和DR小鼠继续最初的高脂肪饮食。结果：将DIO小鼠转换为n-3PUFA或LF饮食后，它们的体重下降到DR和LF小鼠的水平。食物效率从高到低依次为：DIO>；LF>；DR>；DIO-LF>；DIO-n3。应用定量原位杂交技术，我们发现DIO小鼠下丘脑弓状核(Arc)瘦素受体(LR，+290%，p<；0.005)和神经肽Y(NPY，+25%，p<；0.05)基因表达水平高于DR小鼠，而阿片黑素皮质素原(POMC)基因表达水平显著低于DR(-45%，p<；0.01)。改变n-3PUFA饮食和改变LF饮食，基本上恢复到DR水平。结论：本研究结果表明，改变膳食脂肪水平和质量均能有效改变下丘脑神经肽的表达，有效地改善饮食诱导的肥胖。有趣的是，当n-3多不饱和脂肪酸饮食喂给已经肥胖的小鼠时，产生了类似于肥胖抵抗(DR)小鼠的下丘脑基因表达模式。N-3脂肪酸对脑神经肽基因表达的影响是直接的还是间接的，还有待确定。
Aims: Dietary fatty acid profile, independent of caloric percent of fat, is a major regulator of body adiposity. This study examined the effects of dietary fat amount and types on fat storage and hypothalamic gene expression in the mouse model of chronic diet-induced obesity.Methods: The dietary interventions were in twofold: (1) the obesity was induced by a 13-week obesogenic fat diet compared with a low-fat (LF) diet, and (2) the reversibility was tested by using high n-3 polyunsaturated fat (PUFA) and LF diets. Fifty-four C57Bl/6 mice were fed a high-fat (59% in kcal) diet for 13 weeks and then classified as diet-induced obese (DIO) or diet-resistant (DR) mice according to upper and lower tertiles of body weight gain. The DIO mice were then subdivided into three groups for a 6-week secondary dietary intervention. Two of the groups were switched to either a high n-3 PUFA (DIO-n3) or a low-fat (10% in kcal, DIO-LF) diet, whereas the third (controls) and DR mice continued on the initial high-fat diet. Food efficiency was calculated as weekly body weight gain per gram of food intake.Results: After switching the DIO mice to the n-3 PUFA or LF diet, their body weights were reduced to the level of the DR and LF mice. The food efficiencies were, from the highest to lowest, in the order: DIO > LF > DR > DIO-LF > DIO-n3. Using quantitative in situ hybridization, we found that the DIO mice had higher levels of leptin receptor (LR, +290%, p < 0.005) and neuropeptide Y (NPY, +25%, p < 0.05) mRNA expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas the level of pro-opiomelanocortin (POMC) mRNA expression was significantly reduced (-45%, p < 0.01). All effects that were essentially returned to DR levels by the change to the n-3 PUFA diet and, with the exception of a failure to normalize Arc NPY mRNA levels, by the change to LF diet.Conclusions: Taken together, the present results show that both change in level and quality of dietary fat can potently alter hypothalamic neuropeptide expression and result in effective amelioration of diet-induced obesity. Interestingly, the n-3 PUFA diet when fed to already obese mice produced a pattern of hypothalamic gene expression similar to that in obesity resistant (DR) mice. It remains to be determined if the effects of n-3 fatty acids on brain neuropeptide gene expression are direct or indirect.