MOTS-C Peptide
The mot c (methylthioadenosine triphosphate) peptide is a mitochondrial-derived metabolite with broad and diverse physiological actions in many tissues and cells.mots c peptide It is a powerful signal that regulates glucose metabolism, mitochondrial function and fat metabolism, as well as insulin sensitivity, muscle insulin action and physical exercise function.mots c peptide It also exerts anti-inflammatory, neuroprotective and anti-aging effects. It is a ligand for the AMP-activated protein kinase (AMPK) pathway and directly binds to its catalytic subunit. It is activated by energy stress, such as nutrient deprivation and hypoxia. AMPK activation triggers a metabolic signaling cascade that increases intracellular ATP, decreases protein synthesis and promotes glycolysis.

In addition to its role in regulating glucose metabolism, MOTS-c is a potent modulator of inflammation and innate immunity.mots c peptide It is known to inhibit pro-inflammatory cytokines such as TNF-a, IL-1b and IL-6, while increasing the levels of the anti-inflammatory molecule IL-10.mots c peptide MOTS-c also enhances resistance to infection and suppresses the formation of inflammatory macrophage-macrophage aggregates that are associated with bacterial sepsis. In an experimental model of inflammatory injury pain, MOTS-c reduces the levels of pro-inflammatory cytokines induced by formalin and methicillin-resistant Staphylococcus aureus and inhibits the ERK, JNK and P38 MAPK pathways. It also decreases c-Fos expression, a major mediator of inflammatory pain signaling.

Studies have shown that MOTS-c induces a transcriptional response in the nucleus by interacting with PGC-1a, an essential cofactor for mitochondrial biogenesis.mots c peptide This interaction is mediated by a mechanism that involves the AMPK-PGC-1a-ROS axis.mots c peptide The synthesis of ROS and the activation of NF-kB by oxidative stress can activate PGC-1a. PGC-1a is then phosphorylated and deacetylated by AMPK, which can increase its activity. Inhibition of AMPK phosphorylation with compound C or specific siRNA suppresses PGC-1a activation and inhibits the anti-inflammatory effect of MOTS-c.

Moreover, MOTS-c also increases the expression of genes involved in monoacylglycerol and dicarboxylic acid metabolism, and downregulates three pathways of sphingolipid metabolism: ceramide, sphingosine and sphingosine 1-phosphate.mots c peptide These molecules are elevated in T2D and obesity, and MOTS-c improves insulin sensitivity and increases b-oxidation of fatty acids in mice by downregulating these pathways.

Furthermore, a mouse model on a high-fat diet reveals that MOTS-c significantly lowers body weight gain and improves metabolic flexibility and insulin sensitivity by enhancing the expression of the FOXO3A gene.mots c peptide Besides, this peptide inhibits the formation of inflammatory macrophage-macrophage-macrophage aggregates and increases their phagocytic and bactericidal capacity. It also reduces the number of mononuclear osteoblast-like cells that differentiate from myeloid progenitor cells in bone marrow and thereby prevents the formation of multinucleated osteoblasts in a dose-dependent manner. These findings suggest that mot c peptide is a promising candidate for the treatment of obesity, type 2 diabetes and metabolic disorders. All experiments in this article were carried out in accordance with the university of southern California and the University of California, Los Angeles animal care and use committee guidelines. All animals were housed at the Molecular Medicine Research Core facility at the University of Southern California Health Sciences Center.