Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice
Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice
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DOI：
10.1113/jphysiol.2012.233288
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发表时间：
2012-09-01
影响因子：
5.5
通讯作者：
Watt, Matthew J.
中科院分区：
文献类型：
--
作者：
Borg, Melissa L.;Omran, Simin Fallah;Watt, Matthew J.
肥胖的特征是脂肪酸在扩张的脂肪组织以及外周组织（如骨骼肌和肝脏）中的储存增加，并且在这些外周组织中与胰岛素抵抗的发展相关。高脂肪饮食喂养时，中枢神经系统也会产生胰岛素抵抗。下丘脑细胞积累/储存脂质的能力以及肥胖的影响仍不明确。本研究的目的是（1）检测饮食脂肪摄入增加的小鼠以及喂食低脂饮食的肥胖ob/ob小鼠下丘脑中的脂质含量，（2）确定耐力运动训练是否能减少高脂肪饮食小鼠下丘脑中的脂质积累。雄性C57BL/6小鼠分别喂食低脂（LFD）或高脂肪饮食（HFD）12周；ob/ob小鼠维持普通饮食。高脂肪饮食 - 运动（HFD - ex）组小鼠进行12周高脂肪饮食喂养，并接受6周跑步机运动训练（从每天30分钟逐渐增加到70分钟）。通过无偏质谱法评估下丘脑脂质。高脂肪饮食增加了体重和肝脏脂质积累，并导致葡萄糖耐受不良，而高脂肪饮食 - 运动组小鼠体重减轻且葡萄糖耐受性改善。共鉴定和定量了335种脂质分子种类。已知会诱导胰岛素抵抗的脂质，包括神经酰胺（增加22%）、二酰基甘油（增加25%）、溶血磷脂酰胆碱（增加17%）、胆固醇酯（增加60%）和二己糖基神经酰胺（增加33%），在高脂肪饮食组小鼠的下丘脑中相较于低脂饮食组小鼠有所增加。下丘脑中的脂质在运动训练以及ob/ob小鼠中未发生改变，这表明肥胖本身并不会改变下丘脑中的脂质。总体而言，下丘脑中的脂质积累受饮食脂质含量的调节，并且对耐力运动训练的改变具有抵抗性。
Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%up arrow), diacylglycerol (25%up arrow), lysophosphatidylcholine (17%up arrow), cholesterol esters (60%up arrow) and dihexosylceramide (33%up arrow), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.