Genetic architecture of the murine serum metabolome reveals carboxyl esterases as master regulators of circulating fatty acid metabolism.

Carboxyl esterases Ces1 and Ces2 on mouse chromosome 8 are linked to multiple serum lipid classes, acylcarnitines, and acyl-CoAs in 541 Diversity Outbred mice.

• Why it matters: Genetic effects on circulating metabolites can be masked in human studies by sex, diet, age, medication, and environment, motivating model systems that isolate genetic contributions.
• What they did: Using mass spectrometry on 541 Diversity Outbred mice, the study mapped 1,933 mQTL across 240 metabolites, 561 lipids, 43 oxylipins, and 4,465 MS/MS features, including chromosome 8 Ces1/Ces2 associations.
• The result: The resulting high-resolution genetic map, including compartment-specific control versus matched red blood cell mQTL, enables mechanistic hypotheses about circulating fatty acid metabolism regulation.

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