Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance
Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance
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DOI：
10.1073/pnas.0802690105
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发表时间：
2008-05-06
影响因子：
11.1
通讯作者：
Weisinger, Richard S.
中科院分区：
文献类型：
--
作者：
Jayasooriya, Anura P.;Mathai, Michael L.;Weisinger, Richard S.
脂肪组织除了在脂肪储存中发挥作用外，还充当内分泌器官，并且含有功能性肾素-血管紧张素系统（RAS）。血管紧张素转换酶 (ACE) 通过将血管紧张素 I 转化为生物活性肽血管紧张素 II (Ang II)，在 RAS 中发挥关键作用。在本研究中，在ACE基因已被删除（ACE（-/-））的纯合小鼠中确定了靶向RAS对身体能量稳态和葡萄糖耐量的影响，并与野生型同窝小鼠进行了比较。与野生型同窝小鼠相比，ACE(-/-)小鼠体重较低，体脂比例较低，尤其是腹部脂肪。 ACE(-/-) 小鼠的进食状态总能量消耗 (TEE) 和静息能量消耗 (REE) 高于野生型同窝小鼠。 ACE(-/-)小鼠肝脏中与脂肪分解和脂肪酸氧化相关的酶（脂蛋白脂肪酶、肉碱棕榈酰转移酶、长链乙酰辅酶A脱氢酶）的基因表达显着增加，血浆瘦素也降低。相比之下，每日食物摄入量、活动量、进食状态血浆脂质或粪便中脂肪排泄比例没有检测到差异。总之，ACE 活性的降低与体内脂肪积累的减少有关，尤其是腹部脂肪库。 ACE(-/-)小鼠体内脂肪的减少与食物摄入无关，似乎是由于与肝脏中脂肪酸代谢增加相关的高能量消耗，以及葡萄糖耐量增加的额外影响。
In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE(-/-)) and compared with wild-type littermates. Compared with wild-type littermates, ACE(-/-) mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE(-/-) mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE(-/-) mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE(-/-) mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.