Timing of unsaturated fat intake improves insulin sensitivity via the gut microbiota-bile acid axis: a randomized controlled trial

Chunbo Wei, Xiaoqing Xu, Jia Zhang, Xuanyang Wang, Tianshu Han, Yingfeng Zhang, Sijia Pan, Zhu Ming, Ran Li, Fengge Lou, Yu Cheng, Huan Xu, Xingyuan Sun, Guannan Geng, Yujun Pan, Qianmin Liu, Haitao Qi, Xuemin Yan, Keke Dang, Jiaofeng Zhou, Changhao Sun () and Ying Li ()
Additional contact information
Chunbo Wei: Harbin Medical University
Xiaoqing Xu: Harbin Medical University
Jia Zhang: Harbin Medical University
Xuanyang Wang: Harbin Medical University
Tianshu Han: Harbin Medical University
Yingfeng Zhang: Harbin Medical University
Sijia Pan: Harbin Medical University
Zhu Ming: Harbin Medical University
Ran Li: The Second Affiliated Hospital of Harbin Medical University
Fengge Lou: Qiqihar Medical University
Yu Cheng: Qiqihar Medical University
Huan Xu: The First Affiliated Hospital of Harbin Medical University
Xingyuan Sun: The Third Affiliated Hospital of Qiqihar Medical University
Guannan Geng: The First Affiliated Hospital of Harbin Medical University
Yujun Pan: The First Affiliated Hospital of Harbin Medical University
Qianmin Liu: Harbin Medical University
Haitao Qi: Harbin Medical University
Xuemin Yan: Harbin Medical University
Keke Dang: Harbin Medical University
Jiaofeng Zhou: Harbin Medical University
Changhao Sun: Harbin Medical University
Ying Li: Harbin Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The timing of dietary total fat intake influences glucose homeostasis, however, the impact of unsaturated fat (USFA) intake has yet to be explored. This 12-week, double-blind, randomized, controlled, 2 × 2 factorial-designed feeding trial investigated the effects of timing (lunch or dinner) and types of dietary USFA (high monounsaturated fat or polyunsaturated fat diet) intake on glucose metabolism in seventy prediabetes participants (mean age, 57 years). Sixty participants with completed fecal samples were included in the final analysis (n = 15 for each group). Postprandial serum glucose was first primary outcome, postprandial insulin levels and insulin sensitivity indices were co-primary outcomes Secondary outcomes were continuous glucose levels, serum fatty acid profile, gut microbiome (metagenomic sequencing) and fecal metabolites. Results showed no significant differences in postprandial glucose between groups. However, USFA intake at lunch (vs. dinner) improved insulin sensitivity and reduced postprandial insulin and serum free saturated fatty acid (Ptiming 0.05, Pinteraction > 0.05), which was associated with alterations in gut microbiome and bile acid metabolism, regardless of USFA type. In summary, these results suggest that advancing timing of USFA intake improves insulin sensitivity through the gut microbiome and bile acid metabolism. Trial registration: ChiCTR2100045645.

Date: 2025
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DOI: 10.1038/s41467-025-58937-6

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