Patients with a disorder of mitochondrial long-chain fatty acid β-oxidation (FAO) have reduced fasting tolerance and may present with hypoketotic hypoglycemia, hepatomegaly, (cardio)myopathy and rhabdomyolysis. Patients should avoid a catabolic state because it increases reliance on FAO as energy source. It is currently unclear whether weight loss through a reduction of caloric intake is safe in patients with a FAO disorder. We used the long-chain acyl-CoA dehydrogenase knockout (LCAD KO) mouse model to study the impact of dietary restriction (DR) on the plasma metabolite profile and cardiac function. For this, LCAD KO and wild type (WT) mice were subjected to DR (70% of ad libitum chow intake) for 4 weeks and compared to ad libitum chow fed mice. We found that DR had a relatively small impact on the plasma metabolite profile of WT and LCAD KO mice. Echocardiography revealed a small decrease in left ventricular systolic function of LCAD KO mice, which was most noticeable after DR, but there was no evidence of DR-induced cardiac remodeling. Our results suggest that weight loss through DR does not have acute and detrimental consequences in a mouse model for FAO disorders.

患有线粒体长链脂肪酸 β-氧化 (FAO) 疾病的患者禁食耐受性降低，并可能出现低酮性低血糖、肝肿大、（心脏）肌病和横纹肌溶解症。患者应避免分解代谢状态，因为它会增加对粮农组织作为能源的依赖。目前尚不清楚通过减少热量摄入来减轻体重对粮农组织疾病患者是否安全。我们使用长链酰基辅酶 A 脱氢酶敲除 (LCAD KO) 小鼠模型来研究饮食限制 (DR) 对血浆代谢物谱和心脏功能的影响。为此，LCAD KO 和野生型 (WT) 小鼠接受 DR（70% 的随意食物摄入）4 周，并与随意进食的小鼠进行比较。我们发现 DR 对 WT 和 LCAD KO 小鼠的血浆代谢物谱的影响相对较小。超声心动图显示 LCAD KO 小鼠的左心室收缩功能略有下降，这在 DR 后最为明显，但没有证据表明 DR 诱导了心脏重塑。我们的结果表明，通过 DR 减轻体重不会对 FAO 疾病的小鼠模型产生急性和有害的后果。