Insufficient glucose supply is linked to hypothermia upon cold exposure in high-fat diet-fed mice lacking PEMT
Insufficient glucose supply is linked to hypothermia upon cold exposure in high-fat diet-fed mice lacking PEMT
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DOI：
10.1194/jlr.m059287
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发表时间：
2015-09-01
影响因子：
6.5
通讯作者：
Jacobs, Rene L.
中科院分区：
文献类型：
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作者：
Gao, Xia;van der Veen, Jelske N.;Jacobs, Rene L.
缺乏磷脂酰乙醇胺N-甲基转移酶的小鼠（Pemt（-/-）小鼠）被保护免于高脂肪（HF）饮食诱导的肥胖。HF喂养的Pemt（-/-）小鼠显示出更高的耗氧量和产热量，表明更多的能量可能用于产热，并可能解释对饮食诱导的体重增加的抵抗。为了检验这一假设，用HF喂养的Pemt（-/-）和Pemt（+/+）小鼠在4摄氏度的急性冷暴露下进行攻击。出乎意料的是，HF喂养的Pemt（-/-）小鼠在冷暴露的3小时内出现体温过低。相比之下，具有相似体重的Chow喂养的Pemt（-/-）小鼠保持体温。缺乏PEMT并不损害骨骼肌或棕色脂肪组织的产热能力。Pemt基因型未改变血浆儿茶酚胺，Pemt（-/-）小鼠棕色和白色脂肪组织的脂解刺激是完整的。HF喂养的Pemt（-/-）小鼠也出现了更高的收缩压，伴随着心输出量减少。补充胆碱可逆转HF喂养的Pemt（-/-）小鼠中冷诱导的体温降低，对血压无影响。HF喂养的Pemt（-/-）小鼠的血糖水平比Pemt（+/+）小鼠低约50%。补充胆碱可使血浆低血糖和参与血管新生的蛋白质表达正常化。我们认为，HF喂养的Pemt（-/-）小鼠的冷诱导低温与由于肝脏葡萄糖产生受损而导致的血浆低血糖有关。
Mice that lack phosphatidylethanolamine N-methyltransferase (Pemt(-/-) mice) are protected from high-fat (HF) diet-induced obesity. HF-fed Pemt(-/-) mice show higher oxygen consumption and heat production, indicating that more energy might be utilized for thermogenesis and might account for the resistance to diet-induced weight gain. To test this hypothesis, HF-fed Pemt(-/-) and Pemt(+/+) mice were challenged with acute cold exposure at 4 degrees C. Unexpectedly, HF-fed Pemt(-/-) mice developed hypothermia within 3 h of cold exposure. In contrast, chow-fed Pemt(-/-) mice, possessing similar body mass, maintained body temperature. Lack of PEMT did not impair the capacity for thermogenesis in skeletal muscle or brown adipose tissue. Plasma catecholamines were not altered by Pemt genotype, and stimulation of lipolysis was intact in brown and white adipose tissue of Pemt(-/-) mice. HF-fed Pemt(-/-) mice also developed higher systolic blood pressure, accompanied by reduced cardiac output. Choline supplementation reversed the cold-induced hypothermia in HF-fed Pemt(-/-) mice with no effect on blood pressure. Plasma glucose levels were approximate to 50% lower in HF-fed Pemt(-/-) mice compared with Pemt(+/+) mice. Choline supplementation normalized plasma hypoglycemia and the expression of proteins involved in gluconeogenesis. We propose that cold-induced hypothermia in HF-fed Pemt(-/-) mice is linked to plasma hypoglycemia due to compromised hepatic glucose production.