Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats.

Abstract

Leptin is involved in the modulation of insulin signaling in peripheral tissues, being closely associated with changes in lipid metabolism. This adipokine modifies inflammatory pathways that can interact with insulin targets in peripheral organs; however, the mechanisms remain unclear. Inflammatory and insulin signaling targets, cytokines, adiponectin, irisin and non-esterified fatty acid (NEFA) levels and enzymes of fatty acid anabolism were studied in the gastrocnemius of chronic centrally infused leptin (L), pair-fed and control rats. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK) was reduced in L rats (59% and 58%, respectively). The phosphorylation of the insulin receptor and Akt and adiponectin and irisin content was increased in L rats (154%, 157%, 308% and 329%, respectively). The levels of glucose-6-phosphate dehydrogenase, the mRNA content of acetyl Co-A carboxylase and NEFA concentrations were diminished in the muscles of L rats (59%, 50% and 61%, respectively). The activation of JNK correlated positively with STAT3 phosphorylation, tumoral necrosis factor-α and NEFA and negatively with irisin and Akt phosphorylation. These data suggest that the activation of insulin signaling targets and a decrease in NEFA content are associated with a reduction in muscle inflammation parameters, suggesting that leptin may integrate these pathways.