Journal article
Cross-organ metabolite production and consumption in healthy and atherogenic conditions
Cell, Vol.188(16), pp.4441-4455.e16
08/07/2025
DOI: 10.1016/j.cell.2025.05.001
PMID: 40436017
Abstract
Mammalian organs continuously produce and consume circulating metabolites for organismal health and survival. However, the landscape of this fundamental process and its perturbation by diet and disease is unknown. Using arteriovenous metabolomics, tissue transcriptomics, and hormone arrays in multiple pathophysiological conditions in pigs, we generated an atlas of 10 cross-organ metabolite production and consumption during fasting/feeding, Western diet, and cardiovascular disease progression induced by low-density lipoprotein receptor (LDLR) deficiency. We discovered numerous instances of feeding-dependent and -independent metabolite production and consumption by organs and proposed mechanisms by which these are disrupted by Western diet via altered metabolite concentration gradients and hormones. Both Western diet and LDLR deficiency trigger the release of bile acids (BAs) by extra-hepatic organs, likely contributing to abnormally elevated circulating BA levels and consequent vascular inflammation and atherosclerosis development. These resources reveal intricate inter-organ metabolic crosstalk across pathophysiological conditions, offering biochemical insights into diet effects and cardiometabolic diseases.
[Display omitted]
•An atlas of organ-specific metabolite production and consumption in pigs•Western diet compromises organ-specific metabolite production and consumption•Metabolite gradients and hormones may regulate metabolite production and consumption•Western diet and hypercholesterolemia induce bile acid release from extra-hepatic organs
An atlas mapping organ-specific metabolite production and consumption across various pathophysiological states in pigs shows impaired metabolic activity across organs by a Western diet or hypercholesterolemia, including abnormal bile acid release from extra-hepatic tissues.
Details
- Title: Subtitle
- Cross-organ metabolite production and consumption in healthy and atherogenic conditions
- Creators
- Hosung Bae - University of California, IrvineSunhee Jung - University of California, IrvineJohnny Le - University of California, IrvineIan Tamburini - University of California, IrvineJoohwan Kim - University of California, IrvineEric Wang - University of California, IrvineWon-Suk Song - University of California, IrvineWonsuk Choi - University of California, IrvineKi-Hong Jang - University of California, IrvineTaekyung Kang - University of California, IrvineMiranda L. Lopez - University of California, IrvineCuauhtemoc Ramirez - University of California, IrvineIpsita Mohanty - University of California San DiegoMiranda E. Kelly - University of California, IrvineJessie Kim - University of California, IrvineRaymond Kim - University of California, IrvineSang Hee Park - University of California, IrvineJongwon Baek - University of California, IrvineBryan Mendez - University of California, IrvinePaul Petrus - University of California, IrvineThomas Q. de Aguiar Vallim - University of California, Los AngelesDequina A. Nicholas - University of California, IrvineQuinton Smith - University of California, IrvineGina Lee - University of California, IrvineMarcus Seldin - University of California, IrvineCholsoon Jang - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.188(16), pp.4441-4455.e16
- DOI
- 10.1016/j.cell.2025.05.001
- PMID
- 40436017
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/07/2025
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217032102771
Metrics
2 Record Views