Key result
Sestrin2 overexpression alleviates obesity-associated HFpEF by activating adaptive IRE1α-XBP1 signaling and restoring metabolic homeostasis.
Why the study?
The mechanisms by which Sestrin2 mitigates obesity-associated HFpEF through adaptive IRE1α-XBP1 signaling and redox regulation were not fully understood.
Does Sestrin2 overexpression mitigate obesity-associated HFpEF?
Does Sestrin2 overexpression mitigate obesity-associated HFpEF?
Sestrin2 overexpression mitigates obesity-associated HFpEF in preclinical models by modulating ER-mitochondrial stress adaptation and improving redox homeostasis.
These preclinical observations warrant no clinical action; leaves open therapeutic targeting of Sigmar1/Sestrin2 in human cardiovascular disease.
, suggesting the involvement of Sigmar1 in endoplasmic reticulum-mitochondrial stress adaptation. In addition, Sestrin2 overexpression enhances AMPK activation, increases acetyl-CoA carboxylase (AAC) and eNOS phosphorylation, suppresses mTOR signaling, enhances Nrf2-HO-1 antioxidant responses, and reduces inflammatory marker expression and mitochondrial ROS production. Metabolomic analysis further reveals partial alterations in metabolites associated with endoplasmic reticulum stress and redox homeostasis. Collectively, these findings suggest that Sestrin2 alleviates obesity-associated HFpEF and is associated with the activation of adaptive IRE1α-XBP1 signaling involving Sigmar1, together with improved metabolic and redox homeostasis.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2026) studied Obesity-associated HFpEF. Sestrin2 overexpression was evaluated. Sestrin2 overexpression alleviates obesity-associated HFpEF by activating adaptive IRE1α-XBP1 signaling and improving metabolic and redox homeostasis.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: