Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model.

Experimental study using a high-fat diet and streptozotocin-induced Type 2 diabetes rat model to investigate MOTS-c effects on inflammation.

“In this study, we investigated the effects of MOTS‐c treatment on leucine‐rich repeat and pyrin domain‐containing receptor 3 (NLRP3) inflammasome activity in a high‐fat diet and streptozotocin‐induced T2DM rat model.”

Male Wistar rats assigned to control, untreated diabetic, or treated diabetic groups.

“Male Wistar rats (6–7 weeks old, 150–200 g) were purchased from the animal facility (Vernon Jansen Unit) at The University of Auckland.”

Total of 30 rats distributed across three groups with unequal sizes due to exclusions.

“The rats were randomly assigned to three groups: control (n = 12), untreated diabetic (n = 7) and treated diabetic (n = 11).”

15 weeks total, including 15 weeks of high-fat diet, streptozotocin induction at week 8, and 3 weeks of MOTS-c treatment starting at week 12.

“Rats were fed with a high‐fat diet (HFD, 43% digestible energy from lipids, SF04‐001, Specialty Feeds, Glen Forrest WA, Australia) for a total duration of 15 weeks and received a low‐dose intraperitoneal injection of streptozotocin (STZ, 25 mg/kg, in citrate buffer pH 4) at week 8 post‐HFD feeding.”

MOTS-c treatment significantly reduced fasting blood glucose and circulating C-reactive protein levels in diabetic rats.

“MOTS‐c treatment significantly reduced fasting blood glucose and circulating C‐reactive protein levels, while selectively modulating plasma inflammatory cytokines, including interleukin (IL)‐10 and IL‐1β.”

MOTS-c administration reduced levels of NLRP3, ASC, and cleaved caspase-1 in left ventricular tissue.

“Immunohistochemical analysis revealed reduced levels of NLRP3, apoptosis‐associated speck‐like protein containing a caspase activation and recruitment domain (ASC), and cleaved caspase‐1 in left ventricular tissue following MOTS‐c administration.”

Correlation analyses linked IL-18 and IL-1β with elevated markers including low-density lipoprotein and uric acid.

“Correlation analyses linked IL‐18 and IL‐1β with elevated markers, including low‐density lipoprotein and uric acid, suggesting interplay between overall health and inflammasome activity.”

The study used only male Wistar rats, did not assess cell-type-specific responses, and lacked echocardiographic measurements of cardiac contractile function.

“Therefore, the exclusive use of male Wistar rats may limit the applicability of our findings to females or to genetically diverse populations.”