Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands; Top Institute Food and Nutrition (TiFN), Wageningen, The Netherlands.
Top Institute Food and Nutrition (TiFN), Wageningen, The Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
Am J Clin Nutr. 2024 Aug;120(2):347-359. doi: 10.1016/j.ajcnut.2024.05.027. Epub 2024 Jun 6.
We previously showed that dietary intervention effects on cardiometabolic health were driven by tissue-specific insulin resistance (IR) phenotype: individuals with predominant muscle IR (MIR) benefited more from a low-fat, high-protein, and high-fiber (LFHP) diet, whereas individuals with predominant liver insulin resistance (LIR) benefited more from a high-monounsaturated fatty acid (HMUFA) diet.
To further characterize the effects of LFHP and HMUFA diets and their interaction with tissue-specific IR, we investigated dietary intervention effects on fasting and postprandial plasma metabolite profile.
Adults with MIR or LIR (40-75 y, BMI 25-40 kg/m) were randomly assigned to a 12-wk HMUFA or LFHP diet (n = 242). After the exclusion of statin use, 214 participants were included in this prespecified secondary analysis. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, and 240 min) a high-fat mixed meal for quantification of 247 metabolite measures using nuclear magnetic resonance spectroscopy.
A larger reduction in fasting VLDL-triacylglycerol (TAG) and VLDL particle size was observed in individuals with MIR following the LFHP diet and those with LIR following the HMUFA diet, although no longer statistically significant after false discovery rate (FDR) adjustment. No IR phenotype-by-diet interactions were found for postprandial plasma metabolites assessed as total area under the curve (tAUC). Irrespective of IR phenotype, the LFHP diet induced greater reductions in postprandial plasma tAUC of the larger VLDL particles and small HDL particles, and TAG content in most VLDL subclasses and the smaller LDL and HDL subclasses (for example, VLDL-TAG tAUC standardized mean change [95% CI] LFHP = -0.29 [-0.43, -0.16] compared with HMUFA = -0.04 [-0.16, 0.09]; FDR-adjusted P for diet × time = 0.041).
Diet effects on plasma metabolite profiles were more pronounced than phenotype-by-diet interactions. An LFHP diet may be more effective than an HMUFA diet for reducing cardiometabolic risk in individuals with tissue-specific IR, irrespective of IR phenotype. Am J Clin Nutr 20xx;x:xx. This trial was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT03708419?term=NCT03708419&rank=1) as NCT03708419 and CCMO registration (https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=3969AABCD9BA27FEC12587F1001BCC65) as NL63768.068.17.
我们之前的研究表明，饮食干预对心脏代谢健康的影响取决于组织特异性胰岛素抵抗（IR）表型：主要表现为肌肉 IR（MIR）的个体从低脂肪、高蛋白和高纤维（LFHP）饮食中获益更多，而主要表现为肝脏胰岛素抵抗（LIR）的个体从富含单不饱和脂肪酸（HMUFA）的饮食中获益更多。
为了进一步研究 LFHP 和 HMUFA 饮食及其与组织特异性 IR 的相互作用对空腹和餐后血浆代谢物谱的影响，我们调查了饮食干预对空腹和餐后血浆代谢物谱的影响。
40-75 岁、BMI 为 25-40 kg/m2 的 MIR 或 LIR 成年人被随机分配到 12 周的 HMUFA 或 LFHP 饮食（n = 242）。在排除使用他汀类药物后，214 名参与者被纳入本预先指定的二次分析。在高脂肪混合餐前后（T = 0 和 T = 30、60、120 和 240 分钟）采集血浆样本，使用核磁共振光谱法测定 247 种代谢物指标的 247 种代谢物指标。
与 HMUFA 饮食相比，MIR 个体的空腹 VLDL-三酰甘油（TAG）和 VLDL 颗粒大小的降低更为明显，而 LIR 个体的 LFHP 饮食更为明显，尽管在经过错误发现率（FDR）调整后不再具有统计学意义。无论 IR 表型如何，在评估总曲线下面积（tAUC）的餐后血浆代谢物方面，均未发现 IR 表型与饮食之间的相互作用。无论 IR 表型如何，LFHP 饮食均可更大程度地降低餐后更大 VLDL 颗粒和小 HDL 颗粒的 tAUC，以及大多数 VLDL 亚类和较小的 LDL 和 HDL 亚类的 TAG 含量（例如，与 HMUFA 相比，VLDL-TAG tAUC 标准化平均变化[95%CI]LFHP = -0.29 [-0.43，-0.16] vs HMUFA = -0.04 [-0.16，0.09]；饮食×时间的 FDR 调整后 P 值= 0.041）。
饮食对血浆代谢物谱的影响比表型与饮食的相互作用更为明显。LFHP 饮食可能比 HMUFA 饮食更能有效降低组织特异性 IR 个体的心脏代谢风险，无论 IR 表型如何。Am J Clin Nutr 20xx；x：xx。本试验在临床试验.gov 注册（https://clinicaltrials.gov/study/NCT03708419?term=NCT03708419&rank=1），注册号为 NCT03708419，在 CCMO 注册（https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=3969AABCD9BA27FEC12587F1001BCC65），注册号为 NL63768.068.17。
