A study in diabetic rats found that giving the mitochondrial peptide MOTS‑c for eight weeks lowered heart inflammation and damage. It did this by cutting down harmful reactive oxygen species and blocking a key inflammation pathway (ROS/TXNIP/NLRP3). The results suggest MOTS‑c could protect the heart in diabetes, but the work was done in animals and used injections, not oral dosing.

Chronic low-grade inflammation is a characteristic of diabetes, which often culminates in cardiovascular events including myocardial damage, thereby increasing the risk of debilitating cardiac complications. The mitochondria-derived peptide MOTS-c regulates glucose and lipid metabolism while improving insulin resistance, making it a potential candidate for the treatment of diabetes and cardiovascular diseases. We investigated the impact of MOTS-c on cardiac structure and inflammation in diabetic rats induced by a high-sugar-fat diet combined with low-dose streptozotocin (30 mg/kg, i.p.). Our results confirm that high glucose levels activate the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and increase reactive oxygen species (ROS), ultimately leading to myocardial injury. Furthermore, treatment with MOTS-c (0.5 mg/kg/day, i.p.) for 8 weeks reduced the expression of ROS/TXNIP/NLRP3 pathway proteins to inhibit the diabetic myocardial inflammatory response. These findings suggested that MOTS-c alleviates myocardial damage by inhibiting the ROS/TXNIP/NLRP3 pathway.