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

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...

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Main Authors: Vicente Barrios, Santiago Guerra-Cantera, Álvaro Martín-Rivada, Sandra Canelles, Ana Campillo-Calatayud, Eduardo Arilla-Ferreiro, Laura M. Frago, Julie A. Chowen, Jesús Argente
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/7/1465
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author Vicente Barrios
Santiago Guerra-Cantera
Álvaro Martín-Rivada
Sandra Canelles
Ana Campillo-Calatayud
Eduardo Arilla-Ferreiro
Laura M. Frago
Julie A. Chowen
Jesús Argente
author_facet Vicente Barrios
Santiago Guerra-Cantera
Álvaro Martín-Rivada
Sandra Canelles
Ana Campillo-Calatayud
Eduardo Arilla-Ferreiro
Laura M. Frago
Julie A. Chowen
Jesús Argente
author_sort Vicente Barrios
collection DOAJ
description 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 <i>N</i>-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.
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spelling doaj.art-5f3806f5c94640359bef140533e32ab02023-11-30T22:49:40ZengMDPI AGBiomedicines2227-90592022-06-01107146510.3390/biomedicines10071465Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male RatsVicente Barrios0Santiago Guerra-Cantera1Álvaro Martín-Rivada2Sandra Canelles3Ana Campillo-Calatayud4Eduardo Arilla-Ferreiro5Laura M. Frago6Julie A. Chowen7Jesús Argente8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainBiochemical Unit, Department of Biological Systems, Faculty of Medicine, Universidad de Alcalá, E-28871 Alcalá de Henares, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, SpainLeptin 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 <i>N</i>-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.https://www.mdpi.com/2227-9059/10/7/1465adiponectincytokinegastrocnemiusinflammationleptinNEFA
spellingShingle Vicente Barrios
Santiago Guerra-Cantera
Álvaro Martín-Rivada
Sandra Canelles
Ana Campillo-Calatayud
Eduardo Arilla-Ferreiro
Laura M. Frago
Julie A. Chowen
Jesús Argente
Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
Biomedicines
adiponectin
cytokine
gastrocnemius
inflammation
leptin
NEFA
title Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
title_full Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
title_fullStr Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
title_full_unstemmed Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
title_short Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats
title_sort chronic central leptin infusion promotes an anti inflammatory cytokine profile related to the activation of insulin signaling in the gastrocnemius of male rats
topic adiponectin
cytokine
gastrocnemius
inflammation
leptin
NEFA
url https://www.mdpi.com/2227-9059/10/7/1465
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