Key result
Betulinic acid attenuates obesity-induced cardiac remodelling, oxidative injury, and iron overload in preclinical models.
Why the study?
Does oral betulinic acid (40 mg/kg for 6 weeks) attenuate obesity-induced myocardial injury and cardiac remodelling in male Sprague-Dawley rats fed a high-fat diet?
Does oral betulinic acid (40 mg/kg for 6 weeks) attenuate obesity-induced myocardial injury and cardiac remodelling in male Sprague-Dawley rats fed a high-fat diet?
In a rat model of high-fat diet-induced obesity, betulinic acid attenuated obesity-associated cardiac remodelling by modulating mitochondrial quality control, ferroptosis-associated signalling, and calcium-regulatory pathways.
Betulinic acid may attenuate preclinical OACR via mitochondrial/ferroptosis pathways; leaves open clinical translation and human trials.
Obesity-associated cardiac remodelling (OACR) is characterized by metabolic, structural, mitochondrial, oxidative, and molecular alterations that may contribute to progressive cardiac dysfunction. However, the interplay among mitochondrial quality control, ferroptosis, and calcium homeostasis in obesity-associated cardiac injury and remodelling remains incompletely understood. This study investigated whether betulinic acid (BA) attenuates obesity-induced myocardial injury by modulating these interconnected pathways. Male Sprague-Dawley rats were fed a high-fat diet (HFD) for 16 weeks to induce cardiac injury and remodelling and treated with BA (40 mg/kg, orally) for 6 weeks. Cardiac morphology, metabolic parameters, myocardial bioenergetic parameters, oxidative stress, iron homeostasis, and markers associated with mitochondrial quality control, mitochondrial dynamics, ferroptosis, and calcium regulation were assessed using biochemical, histopathological, mRNA, and protein expression analyses. Molecular docking provided hypothesis-generating predictions of potential interactions between BA and selected regulatory proteins. HFD-induced obesity was associated with alterations in mitochondrial quality-control, ferroptosis-associated, and calcium-regulatory signalling markers, including changes in the SERCA2a-CaMKIIδ axis. BA improved metabolic abnormalities, increased myocardial ATP content and the NAD⁺/NADH ratio, and attenuated oxidative injury and iron accumulation. These effects were accompanied by increased PINK1, Parkin, MFN2, GPX4, SLC7A11, and SERCA2a expression and decreased DRP1, ACSL4, and CaMKIIδ expression. BA attenuated OACR, accompanied by changes in mitochondrial quality-control, ferroptosis-associated, and calcium-regulatory proteins. These findings indicate that modulation of these interconnected pathways may contribute to the attenuation of OACR.
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Uddandrao et al. (2026) studied Obesity-associated cardiac remodelling. Betulinic acid vs. High-fat diet untreated control was evaluated on Obesity-associated cardiac remodelling, metabolic parameters, myocardial bioenergetics, oxidative stress, iron homeostasis, and pathway protein expression. Betulinic acid (40 mg/kg for 6 weeks) attenuated obesity-associated cardiac remodelling, oxidative injury, and iron accumulation in high-fat diet-fed rats.
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