A multi-tiered workflow for examining organic acid profiles delineates tissue-specific changes in fatty acyl partitioning during aging

  • Cell Rep Methods. 2026 May 18;6(5):101413. doi: 10.1016/j.crmeth.2026.101413.
Zhiyang Zhou  1 ,  Chenyin Cao  2 ,  Taochao Lu  1 ,  Yuyuan Ruan  1 ,  Bowen Li  1 ,  Mingjun Cao  3 ,  Luyue Mo  4 ,  Guanghou Shui  5 ,  Sin Man Lam  6
Affiliations
  • 1. LipidALL Technologies Company Limited, Jiangsu Provincial Key Laboratory of Molecular Targets and Intervention for Metabolic Diseases, Changzhou 213022, China.
  • 2. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China.
  • 3. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 4. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
  • 5. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China. Electronic address: [email protected].
  • 6. Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China; LipidALL Technologies Company Limited, Jiangsu Provincial Key Laboratory of Molecular Targets and Intervention for Metabolic Diseases, Changzhou 213022, China. Electronic address: [email protected].
PMID: 42019501 DOI: 10.1016/j.crmeth.2026.101413
Abstract

Fatty acids (FAs), as the predominant organic acids, form a major component of the metabolome. We present a multi-tiered method that comprehensively captures FA diversity-including chain lengths (C2-C34), unsaturation, isomers, and endogenous forms-within a single biological specimen. This workflow quantifies the broadest range of free FAs reported to date. Integrated with two complementary tiers profiling the total FA pool from alkaline hydrolysis and esterified acyl compositions across lipid classes, our multi-tiered workflow enables the investigation of differential fatty acyl partitioning. Applying this platform to quantify >540 unique lipids (free and esterified forms) and polar carboxylic acids, we investigated FA remodeling in the brain, retina (eyeball), and skeletal muscles of young and aged mice. We found that aged glycolytic tissues preferentially partition odd-chain and diunsaturated FAs (with lower β-oxidizability) into triacylglycerols. Additionally, aging shifts the FA18:1 partitioning into diacylglycerols over anionic Phospholipids, which may mitigate pro-aging lipid signatures in the skeletal muscle.

Keywords
CP: metabolism; LCFA; SCFA; VLCFA; aging; brain aging; fatty acids; lipidomics; organic acids; skeletal muscle aging.
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