To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARα) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( ± clofibrate) × 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-¹⁴C] palmitic acid (1 mM) as a substrate (0.265 μCi/μmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 μM) or acetoacetate-CoA deacylase (iodoacetamide, 50 μM). Without clofibrate stimulation, ¹⁴C accumulation in CO₂ was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased ¹⁴C-ASP (P < 0.0001) above all other treatments, regardless of clofibrate treatment. The percentage of ¹⁴C in CO₂ was higher (P = 0.0023) in TC5 than in the control group. From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA (product of β-oxidation) via alteration of TCA cycle activity, but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα. In addition, the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.

为了研究增加三羧酸 (TCA) 循环活性和生酮能力是否会增加由过氧化物酶体增殖物激活受体-α (PPARα) 激动剂氯贝丁酯诱导的脂肪酸 (FA) 氧化，将哺乳的新生仔猪 ( n  = 54) 分配给 8遵循 2 (± clofibrate) × 4（甘油琥珀酸酯 [SUC]、2-甲基戊酸甘油三酯 [T2M]、戊酸 [TC5] 和己酸 [TC6]）析因设计的组。每组喂食含有 0% 或 0.35% 氯贝丁酯（wt/wt，干物质基础）和 5% SUC、T2M、TC5 或 TC6 的等热量配方奶粉 5 天。另外 6 头猪作为新生对照。^{使用 [ 1-14} ] 在第 6 天收集的新鲜肝脏匀浆中检测脂肪酸氧化C] 棕榈酸 (1 mM) 作为底物 (0.265 μCi/μmol)。在不存在或存在 L-肉碱 (1 mM) 或 3-羟基-3-甲基戊二酰辅酶 A 合酶抑制剂 (L659699, 1.6 μM) 或乙酰乙酸-CoA 脱酰酶 (碘乙酰胺, 50 μM) 的情况下进行测量。在没有氯贝特刺激的情况下，饲喂含有 T2M 和 TC5 的日粮的仔猪在 CO _2中的¹⁴ C 积累高于 SUC，但与饲喂 TC6 的仔猪相似。在安妥明刺激下，饲喂 TC5 的仔猪匀浆中的积累也高于所有其他日粮处理。 对于酸溶性产品 (ASP) ，观察到氯贝特和肉碱或抑制剂之间的相互作用 ( P = 0.0004)。体外添加肉毒碱增加¹⁴ C-ASP ( P < 0.0001) 高于所有其他治疗，无论氯贝特治疗如何。TC5中 CO _2中¹⁴ C的百分比高于对照组 ( P  = 0.0023)。根据这些结果，我们表明饮食补充回补和生酮 FA 可以影响 FA 氧化并通过改变 TCA 循环活性来改变乙酰辅酶 A（β-氧化产物）的代谢，但这种修饰对肝脏 FA 没有显着影响PPARα 诱导的氧化能力。此外，肉碱的可用性是维持新生儿期 FA 氧化的关键因素。