Treatment with recombinant Sirt1 rewires the cardiac lipidome and rescues diabetes-related metabolic cardiomyopathy
Authors' conclusion
In the db/db mouse model of MCM, chronic exogenous rSirt1 supplementation rescued cardiac function. This was associated with a modulation of the myocardial lipidome and a downregulation of genes involved in lipid metabolism, trafficking, inflammation, and PPARG signaling. These findings were confirmed in the human diabetic myocardium. Treatments that increase Sirt1 levels may represent a promising strategy to prevent myocardial lipid abnormalities and MCM development.
Study context
- Population
- db/db mice (established model of metabolic cardiomyopathy (MCM)); H9c2 cardiomyocytes exposed to hyperglycaemia; myocardial samples from diabetic and nondiabetic patients
- Comparison
- Intraperitoneal recombinant Sirt1 (rSirt1) vs vehicle for 4 weeks in db/db mice, compared with db/ + littermates
- Outcome
- Cardiac function and lipidome
- Follow-up
- End of 4-week treatment
Methodological detailsdb/db mouse model, in vitro H9c2 cardiomyocytes, human myocardial samples
- Db/db mouse model
- In vitro H9c2 cardiomyocytes
- Human myocardial samples
Main finding
As reported in the abstract
end of 4-week treatment
- rSirt1 restored cardiac Sirt1 levels and preserved cardiac performance, improving LVEF, fractional shortening and diastolic function (E/A ratio)
- rSirt1 reduced medium and long-chain, long-chain and saturated-only triacylglycerols and increased DHA-containing triacylglycerols in LV samples
- Cd36, Acox3, Pparg, Ncoa3 and Ppara downregulated by rSirt1 in vitro and in vivo
Further findings
Human myocardium
- Reduced cardiac Sirt1 expression associated with higher intramyocardial triacylglycerols and PPARG-related genes
Original publication
Treatment with recombinant Sirt1 rewires the cardiac lipidome and rescues diabetes-related metabolic cardiomyopathy. Cardiovasc Diabetol. Published 13 November 2023. doi:10.
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