Vitamin K2 reprograms the multi-organ transcriptional landscape in mice with high-fat diet-induced obesity

Abstract

Vitamin K2 (VK2) shows promise as a nutritional intervention for obesity-related disorders, but its mechanisms of action in obesity and associated phenotypes are not yet fully understood. This study aims to elucidate the rescue effects of VK2 on multiple tissues during obesity. Twenty-eight 8-week-old male C57BL6/N mice are divided into four groups and fed a high-fat diet or normal diet for 16 weeks, receiving either menaquinone-7 (MK-7) or soybean oil solvent via gavage. RNA sequencing of brain, colon, muscle, heart, kidney, and liver tissues constructed a multi-organ transcriptional profile. The “rescue differentially expressed genes (DEGs)” are identified and tissue–tissue communication is analyzed. VK2 improves the biochemical profile in high-fat diet-induced obesity. Following VK2 intervention, the brain and kidneys exhibit more changes in autophagy, neurodegenerative diseases, energy metabolism, and immune response pathways. VK2 rescues over 10% of abnormally expressed genes, with most being fully restored. These rescue genes exhibit tissue-specific biological effects, including neuropeptide signaling and neuron ensheathment in the brain; triglyceride metabolism and carboxylic acid catabolism in the colon; microvillus organization and vascular permeability regulation in the heart; regulation of immune processes and collagen biosynthesis in the kidney; transforming growth factor-beta receptor signaling, iron transport and homeostasis in the liver; and muscle contraction, ATP transport, and filament sliding in the muscle. VK2 eliminates elevated ligand–receptor signals in immune response pathways and promotes the tissue–tissue signaling network to approach healthy control levels. VK2 significantly rescues the multi-organ transcriptome and restores tissue-specific pathways in high-fat diet-induced obese mice, providing the molecular mechanisms countering metabolic disorders.

Graphical abstract: Vitamin K2 reprograms the multi-organ transcriptional landscape in mice with high-fat diet-induced obesity

Supplementary files

Article information

Article type
Paper
Submitted
03 Apr 2025
Accepted
05 Jul 2025
First published
10 Jul 2025

Food Funct., 2025, Advance Article

Vitamin K2 reprograms the multi-organ transcriptional landscape in mice with high-fat diet-induced obesity

X. Wang, Y. Zhang, L. Liu, H. Ma, C. Wei, X. Xu, J. Zhang, S. Pan, Y. Zhang, J. Chen, L. Duan, G. Geng, K. Dang, H. Xie, G. Wang, L. Li, R. Li and Y. Li, Food Funct., 2025, Advance Article , DOI: 10.1039/D5FO01613D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements