mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy
and failing rat hearts.
Authors Goedeke L, Ma Y, Gaspar RC, Nasiri A, Lee J, Zhang D, Galsgaard KD, Hu X, Zhang
J, Guerrera N, Li X, LaMoia T, Hubbard BT, Haedersdal S, Wu X, Stack J, Dufour
S, Butrico GM, Kahn M, Perry RJ, Cline GW, Young LH, Shulman GI
Submitted By Submitted Externally on 2/7/2025
Status Published
Journal The Journal of clinical investigation
Year 2024
Date Published 12/1/2024
Volume : Pages 134 : Not Specified
PubMed Reference 39680452
Abstract Previous studies highlight the potential for sodium-glucose cotransporter type 2
(SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure
by increasing plasma ketones and shifting myocardial fuel utilization toward
ketone oxidation. However, SGLT2i have multiple in vivo effects and the
differential impact of SGLT2i treatment and ketone supplementation on cardiac
metabolism remains unclear. Here, using gas chromatography-mass spectrometry
(GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS)
methodology combined with infusions of [13C6]glucose or [13C4]ßOHB, we
demonstrate that acute SGLT2 inhibition with dapagliflozin shifts relative rates
of myocardial mitochondrial metabolism toward ketone oxidation, decreasing
pyruvate oxidation with little effect on fatty acid oxidation in awake rats.
Shifts in myocardial ketone oxidation persisted when plasma glucose levels were
maintained. In contrast, acute ßOHB infusion similarly augmented ketone
oxidation, but markedly reduced fatty acid oxidation and did not alter glucose
uptake or pyruvate oxidation. After inducing heart failure, dapagliflozin
increased relative rates of ketone and fatty acid oxidation, but decreased
pyruvate oxidation. Dapagliflozin increased mitochondrial redox and reduced
myocardial oxidative stress in heart failure, which was associated with
improvements in left ventricular ejection fraction after 3 weeks of treatment.
Thus, SGLT2i have pleiotropic effects on systemic and heart metabolism, which
are distinct from ketone supplementation and may contribute to the long-term
cardioprotective benefits of SGLT2i.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.