<i>Chlamydomonas reinhardtii</i> (Red) Rich in Protoporphyrin IX Exerts Anti‐Diabetic Effects in Liver Tissue

The metabolites derived from microalgae have been attributed with various nutritional and medicinal properties. Therefore, our research focused on exploring the potential benefits of Chlamydomonas reinhardtii (red) for type 2 diabetes mellitus (T2DM) patients. Mice were subjected to a high-fat diet and low-dose streptozotocin injection to develop T2DM. These diabetic mice were then treated orally with either 1% sodium carboxymethylcellulose or C. reinhardtii (red) at 1-3 g/kg BW/day for 4 weeks. Liver sections were stained with hematoxylin-eosin and oil red to assess pathological changes and lipid deposition. Serum inflammatory factors were measured using ELISA, and oxidative stress indicators were evaluated with commercial kits. C. reinhardtii (red) treatment significantly improved fasting glucose, body weight, triglycerides, LDL-C, and enhanced glucose tolerance and insulin sensitivity. It also reduced liver damage and lipid deposition. The treatment decreased G-6-Pase and PEPCK protein expression and modulated the SOCS2/JAK2/STAT5 pathway. RNA-seq analysis showed 972 differentially expressed genes in treated diabetic mice. KEGG analysis indicated the involvement of lipid metabolism, inflammation, and multiple pathways in the effects of C. reinhardtii (red). C. reinhardtii (red) might counteract T2DM by inhibiting gluconeogenesis and modulating key metabolic pathways, suggesting its potential as a dietary intervention for patients.