Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK; Aston Medical School, Aston University, Birmingham B4 7ET, UK.
Clin Nutr. 2024 Oct;43(10):2305-2315. doi: 10.1016/j.clnu.2024.08.028. Epub 2024 Aug 24.
We have previously demonstrated that dietary saturated fatty acids (SFA), when compared to polyunsaturated fatty acids (PUFA), are preferentially partitioned into oxidation pathways. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated.
To investigate whether an acute upregulation of hepatic DNL influences dietary FA partitioning into oxidation pathways.
20 healthy volunteers (11 females) underwent a fasting baseline visit followed by two study days, 2-weeks apart. Prior to each study day, participants consumed an isocaloric high-carbohydrate diet (to upregulate hepatic DNL) for 3-days. On the two study days, participants consumed an identical standardised test meal that contained either [UC]palmitate or [UC]linoleate, in random order, to trace the fate of dietary FA. Blood and breath samples were collected over a 6h postprandial period and C enrichment in breath CO and plasma lipid fractions were measured using gas-chromatography-combustion-isotope ratio mass spectrometry.
Compared to the baseline visit, fasting plasma triglyceride concentrations and markers of hepatic DNL, the lipogenic and stearyl-CoA desaturase indices, were significantly (p < 0.05) increased after consumption of the high-carbohydrate diet. Appearance of C in expired CO and tracer recovery were significantly (p < 0.05) higher after consumption of the meal containing [UC]linoleate compared to [UC]palmitate (5.1 ± 0.5% vs. 3.7 ± 0.4%), respectively. Incorporation of C into the plasma triglyceride and non-esterified fatty acid pool was significantly (p < 0.001) greater for [UC]palmitate compared to [UC]linoleate.
Dietary PUFA compared to SFA appear to be preferentially partitioned into oxidation pathways during an acute upregulation of hepatic DNL, thus consumption of a PUFA-enriched diet may help mitigate intrahepatic triglyceride accumulation in individuals at risk of cardiometabolic disease.
我们之前已经证明，与多不饱和脂肪酸（PUFA）相比，膳食饱和脂肪酸（SFA）优先分配到氧化途径中。然而，当肝细胞代谢向脂肪酸（FA）酯化而不是氧化转移时，这种优先处理是否仍然存在，例如当肝从头合成（DNL）上调时，目前尚不清楚。
研究急性上调肝 DNL 是否影响膳食 FA 分配到氧化途径中。
20 名健康志愿者（11 名女性）进行了空腹基线访视，然后每隔两周进行两次研究。在每次研究前，参与者连续 3 天摄入高碳水化合物饮食（上调肝 DNL）。在两天的研究中，参与者随机顺序摄入相同的标准化测试餐，其中包含 [UC]棕榈酸或 [UC]亚油酸，以追踪膳食 FA 的命运。在餐后 6 小时内采集血液和呼吸样本，并使用气相色谱-燃烧-同位素比质谱法测量呼吸 CO 中的 C 富集和血浆脂质分数。
与基线访问相比，空腹血浆甘油三酯浓度和肝 DNL 的标志物，即生脂和硬脂酰辅酶 A 去饱和酶指数，在高碳水化合物饮食后显著（p<0.05）升高。与 [UC]棕榈酸相比，摄入含有 [UC]亚油酸的餐后，呼出 CO 中 C 的出现和示踪剂回收率显著（p<0.05）更高（分别为 5.1±0.5%比 3.7±0.4%）。[UC]棕榈酸与 [UC]亚油酸相比，C 掺入血浆甘油三酯和非酯化脂肪酸池的比例显著（p<0.001）更高。
与 SFA 相比，膳食 PUFA 似乎在肝 DNL 急性上调期间优先分配到氧化途径中，因此，摄入富含 PUFA 的饮食可能有助于减轻代谢疾病风险个体的肝内甘油三酯积累。
