Butyrate counteracts maternal obesity-induced cardiac defects by promoting PLEKHG3-actin binding.

Butyrate supplementation rescues maternal obesity-induced fetal cardiac abnormalities by enhancing PLEKHG3-actin interactions in mice and human cardiomyocytes.

• Why it matters: Maternal obesity is linked to abnormal cardiac development during gestation, but the metabolic mechanisms behind these defects are not well understood, limiting therapeutic options.
• What they did: Researchers identified reduced butyrate levels in high-fat diet-fed mice and their embryos, and demonstrated that butyrate supplementation restores normal cardiac structure and function using in vivo and in vitro models, including human induced pluripotent stem cell-derived cardiomyocytes and organoids.
• The result: Butyrate binds directly to PLEKHG3, promoting its interaction with F-Actin, which improves contractility and myofibril organization; loss of PLEKHG3 function negates these effects, suggesting butyrate’s potential as a therapy for maternal obesity-related cardiac defects.