Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment
Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflam...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/11/1734 |
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| author | Vicente Barrios Ana Campillo-Calatayud Santiago Guerra-Cantera Sandra Canelles Álvaro Martín-Rivada Laura M. Frago Julie A. Chowen Jesús Argente |
| author_facet | Vicente Barrios Ana Campillo-Calatayud Santiago Guerra-Cantera Sandra Canelles Álvaro Martín-Rivada Laura M. Frago Julie A. Chowen Jesús Argente |
| author_sort | Vicente Barrios |
| collection | DOAJ |
| description | Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels in inguinal fat and liver of chronic central leptin infused (L), pair-fed (PF), and control rats. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was increased in inguinal fat and reduced in liver of L rats. Phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NFkB) was increased in inguinal fat of L rats, together with a pro-inflammatory cytokine profile, while in the liver activation of JNK and NFkB were reduced and an anti-inflammatory pattern was found. Phosphorylation of the insulin receptor, Akt and mechanistic target of rapamycin was decreased in inguinal fat and increased in liver of L rats. There was a direct relationship between pSTAT3 and JNK and a negative correlation of Akt with pSTAT3 and JNK in both tissues. These results indicate that the effects of chronically increased leptin on insulin-related signaling are tissue-specific and suggest that inflammation plays a relevant role in the crosstalk between leptin and insulin signaling. |
| first_indexed | 2024-03-10T05:40:06Z |
| format | Article |
| id | doaj.art-37a369bc6d914d82bc80f0162464c553 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:40:06Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-37a369bc6d914d82bc80f0162464c5532023-11-22T22:35:33ZengMDPI AGBiomolecules2218-273X2021-11-011111173410.3390/biom11111734Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory EnvironmentVicente Barrios0Ana Campillo-Calatayud1Santiago Guerra-Cantera2Sandra Canelles3Álvaro Martín-Rivada4Laura M. Frago5Julie A. Chowen6Jesús Argente7Department 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, 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 modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels in inguinal fat and liver of chronic central leptin infused (L), pair-fed (PF), and control rats. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was increased in inguinal fat and reduced in liver of L rats. Phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NFkB) was increased in inguinal fat of L rats, together with a pro-inflammatory cytokine profile, while in the liver activation of JNK and NFkB were reduced and an anti-inflammatory pattern was found. Phosphorylation of the insulin receptor, Akt and mechanistic target of rapamycin was decreased in inguinal fat and increased in liver of L rats. There was a direct relationship between pSTAT3 and JNK and a negative correlation of Akt with pSTAT3 and JNK in both tissues. These results indicate that the effects of chronically increased leptin on insulin-related signaling are tissue-specific and suggest that inflammation plays a relevant role in the crosstalk between leptin and insulin signaling.https://www.mdpi.com/2218-273X/11/11/1734adipose tissuecytokinesinflammationinsulin signalingleptinliver |
| spellingShingle | Vicente Barrios Ana Campillo-Calatayud Santiago Guerra-Cantera Sandra Canelles Álvaro Martín-Rivada Laura M. Frago Julie A. Chowen Jesús Argente Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment Biomolecules adipose tissue cytokines inflammation insulin signaling leptin liver |
| title | Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment |
| title_full | Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment |
| title_fullStr | Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment |
| title_full_unstemmed | Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment |
| title_short | Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment |
| title_sort | opposite effects of chronic central leptin infusion on activation of insulin signaling pathways in adipose tissue and liver are related to changes in the inflammatory environment |
| topic | adipose tissue cytokines inflammation insulin signaling leptin liver |
| url | https://www.mdpi.com/2218-273X/11/11/1734 |
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