Liver oxylipin profiles in calorie-restricted versus ad libitum mice across aging
In mice, lifelong calorie restriction blunted a mid-life shift toward pro-inflammatory liver oxylipins, preserved EPA-derived epoxy-fatty acids and induced the redox enzyme CYB5R3; these changes coincided with less liver lipid accumulation and a more favorable systemic metabolic profile. [1]
Automatic summary · not editorially reviewed
The key findings
In ad libitum-fed mice, about 9 months appeared as an inflection point toward a pro-inflammatory liver oxylipin state. [1]
Lifelong calorie restriction preserved EPA-derived epoxy-fatty acids and induced the redox enzyme CYB5R3. [1]
The authors nominate CYB5R3-associated redox regulation as a hypothesis for future mechanistic investigation. [1]
The source at a glance
- Study type / format
- Abstract of a preclinical mouse study with age-stratified targeted oxylipin profiling.
- Population / context
- Livers from mice fed ad libitum or with lifelong calorie restriction, profiled across adulthood and aging.
- Summary based on
- Study abstract
- Original publication
- September 18, 2026
Liver lipid mediators in AL versus CR mice
The abstract describes targeted profiling of oxylipins, which are lipid mediators, in livers of mice fed ad libitum (AL) or with lifelong calorie restriction (CR), sampled across adulthood and aging. In AL-fed mice, about 9 months appeared as an inflection point: oxylipin networks shifted toward a pro-inflammatory state, with transient rises in PGE₂, 11-keto-TXB₂, 20-HETE and 5-oxo-ETE and loss of pro-resolving mediators. Later life showed depletion of CYP-derived epoxides and accumulation of soluble epoxide hydrolase-generated diols.
Supporting source [1]
CR blunted mid-life surge and preserved epoxides
Lifelong CR dynamically reprogrammed these trajectories: it blunted the mid-life inflammatory surges, preserved EPA-derived epoxy-fatty acids such as EpETEs, and induced the redox enzyme CYB5R3. The authors suggest CYB5R3 may sustain CYP epoxygenase activity and epoxide output despite reduced enzyme abundance. These oxylipin changes coincided with reduced hepatic lipid accumulation and a more favorable systemic metabolic profile in CR mice.
Supporting source [1]
Hypothesis for future mechanistic work, not proven cause
The authors frame their findings as identifying age- and diet-associated remodeling of the hepatic COX/LOX/CYP oxylipin network, especially the epoxide-diol profile. They nominate CYB5R3-associated redox regulation as a hypothesis for future mechanistic investigation, not as an established mechanism. The described coincidences between oxylipin changes and metabolic measures are associations in mice, not evidence of cause or of human lifespan benefit.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. The work is in mice, and the CYB5R3 link is presented as a hypothesis, not a demonstrated mechanism. The metabolic findings are described as coinciding with oxylipin changes, so they are associations, not proof of cause or of human benefit.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Wei L, Sun D, Huang Y, Ouyang X, Zheng J, Yu Y, Han C, Yang Y, Hong J, Zheng Y. · europepmc.org · September 18, 2026