Kinman Renée P, Kasumov Takhar, Jobbins Kathryn A, Thomas Katherine R, Adams Jillian E, Brunengraber Lisa N, Kutz Gerd, Brewer Wolf-Ulrich, Roe Charles R, Brunengraber Henri
Department of Pediatrics, Case Western Reserve University, Euclid Ave., Cleveland, OH 44106-4954, USA.
Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E860-6. doi: 10.1152/ajpendo.00366.2005. Epub 2006 May 16.
A new chronic treatment for inherited disorders of long-chain fatty acid oxidation involves administering up to one-third of dietary calories as triheptanoin, a medium-odd-chain triglyceride (Roe CR, Sweetman L, Roe DS, David F, and Brunengraber H. J Clin Invest 110: 259-269, 2002). Heptanoate and C(5)-ketone bodies derived from its partial oxidation in liver are precursors of anaplerotic propionyl-CoA in peripheral tissues. It was hypothesized that increasing anaplerosis in peripheral tissues would boost energy production. In the present study, we tested the potential of a triheptanoin emulsion as an intravenous nutrient. Normal rats were infused with triheptanoin intravenously or intraduodenally at up to 40% of caloric requirement. The blood concentration ratio (heptanoate/C(5)-ketone bodies) was high with intravenous and low with intraduodenal triheptanoin infusion. During intravenous infusion of triheptanoin, lipolysis was stimulated but appeared compensated by fatty acid reesterification. During intraduodenal infusion of triheptanoin, lipolysis was not stimulated. Our data support the hypothesis that intravenous triheptanoin could be used to treat decompensated patients with long-chain fatty acid oxidation disorders.
一种针对长链脂肪酸氧化遗传性疾病的新型慢性治疗方法，是给予高达膳食热量三分之一的三庚酸甘油酯（一种中奇链甘油三酯）（Roe CR、Sweetman L、Roe DS、David F和Brunengraber H。《临床研究杂志》110: 259 - 269，2002年）。庚酸以及其在肝脏中部分氧化产生的C(5)-酮体是外周组织中回补性丙酰辅酶A的前体。据推测，增加外周组织中的回补作用会提高能量产生。在本研究中，我们测试了三庚酸甘油酯乳剂作为静脉内营养物的潜力。给正常大鼠静脉内或十二指肠内输注高达热量需求40%的三庚酸甘油酯。静脉内输注三庚酸甘油酯时血浓度比（庚酸/C(5)-酮体）高，十二指肠内输注时则低。在静脉内输注三庚酸甘油酯期间，脂解作用受到刺激，但似乎通过脂肪酸再酯化得到了补偿。在十二指肠内输注三庚酸甘油酯期间，脂解作用未受到刺激。我们的数据支持这样的假说，即静脉内三庚酸甘油酯可用于治疗长链脂肪酸氧化障碍失代偿患者。
