Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling

Leptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibil...

Full description

Bibliographic Details
Main Authors: María E. Casado, Sandra Canelles, Eduardo Arilla-Ferreiro, Laura M. Frago, Vicente Barrios
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/8/7065
_version_ 1797605140524433408
author María E. Casado
Sandra Canelles
Eduardo Arilla-Ferreiro
Laura M. Frago
Vicente Barrios
author_facet María E. Casado
Sandra Canelles
Eduardo Arilla-Ferreiro
Laura M. Frago
Vicente Barrios
author_sort María E. Casado
collection DOAJ
description Leptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibility, we examined the effects of chronic central administration of leptin on the expression of key markers of lipid metabolism and its possible relationship with changes in inflammatory- and insulin-signaling pathways in epididymal adipose tissue. Circulating non-esterified fatty acids and pro- and anti-inflammatory cytokines were also measured. Fifteen male rats were divided into control (C), leptin (L, icv, 12 μg/day for 14 days), and pair-fed (PF) groups. We found a decrease in the activity of glucose-6-phosphate dehydrogenase and malic enzyme in the L group, with no changes in the expression of lipogenic enzymes. A reduction in the expression of lipoprotein lipase and carnitine palmitoyl-transferase-1A, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern, were detected in the epididymal fat of L rats. In conclusion, the decrease in insulin sensitivity and increased pro-inflammatory environment could regulate lipid metabolism, reducing epididymal fat stores in response to central leptin infusion.
first_indexed 2024-03-11T04:56:56Z
format Article
id doaj.art-4487f33869b347fc8c105f11362d9223
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T04:56:56Z
publishDate 2023-04-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-4487f33869b347fc8c105f11362d92232023-11-17T19:34:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248706510.3390/ijms24087065Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin SignalingMaría E. Casado0Sandra Canelles1Eduardo Arilla-Ferreiro2Laura M. Frago3Vicente Barrios4Department of Endocrinology, Instituto de Investigación La Princesa, Hospital Infantil Universitario Niño Jesús, E-28009 Madrid, SpainDepartment of Endocrinology, Instituto de Investigación La Princesa, Hospital Infantil Universitario Niño Jesús, E-28009 Madrid, SpainDepartment of Biological Systems, Faculty of Medicine, Universidad de Alcalá, E-28871 Alcala de Henares, SpainDepartment of Endocrinology, Instituto de Investigación La Princesa, Hospital Infantil Universitario Niño Jesús, E-28009 Madrid, SpainDepartment of Endocrinology, Instituto de Investigación La Princesa, Hospital Infantil Universitario Niño Jesús, E-28009 Madrid, SpainLeptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibility, we examined the effects of chronic central administration of leptin on the expression of key markers of lipid metabolism and its possible relationship with changes in inflammatory- and insulin-signaling pathways in epididymal adipose tissue. Circulating non-esterified fatty acids and pro- and anti-inflammatory cytokines were also measured. Fifteen male rats were divided into control (C), leptin (L, icv, 12 μg/day for 14 days), and pair-fed (PF) groups. We found a decrease in the activity of glucose-6-phosphate dehydrogenase and malic enzyme in the L group, with no changes in the expression of lipogenic enzymes. A reduction in the expression of lipoprotein lipase and carnitine palmitoyl-transferase-1A, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern, were detected in the epididymal fat of L rats. In conclusion, the decrease in insulin sensitivity and increased pro-inflammatory environment could regulate lipid metabolism, reducing epididymal fat stores in response to central leptin infusion.https://www.mdpi.com/1422-0067/24/8/7065adipose tissuecytokinesinflammationinsulin resistanceleptinlipolysis
spellingShingle María E. Casado
Sandra Canelles
Eduardo Arilla-Ferreiro
Laura M. Frago
Vicente Barrios
Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
International Journal of Molecular Sciences
adipose tissue
cytokines
inflammation
insulin resistance
leptin
lipolysis
title Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
title_full Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
title_fullStr Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
title_full_unstemmed Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
title_short Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling
title_sort changes in lipid metabolism enzymes in rat epididymal fat after chronic central leptin infusion are related to alterations in inflammation and insulin signaling
topic adipose tissue
cytokines
inflammation
insulin resistance
leptin
lipolysis
url https://www.mdpi.com/1422-0067/24/8/7065
work_keys_str_mv AT mariaecasado changesinlipidmetabolismenzymesinratepididymalfatafterchroniccentralleptininfusionarerelatedtoalterationsininflammationandinsulinsignaling
AT sandracanelles changesinlipidmetabolismenzymesinratepididymalfatafterchroniccentralleptininfusionarerelatedtoalterationsininflammationandinsulinsignaling
AT eduardoarillaferreiro changesinlipidmetabolismenzymesinratepididymalfatafterchroniccentralleptininfusionarerelatedtoalterationsininflammationandinsulinsignaling
AT lauramfrago changesinlipidmetabolismenzymesinratepididymalfatafterchroniccentralleptininfusionarerelatedtoalterationsininflammationandinsulinsignaling
AT vicentebarrios changesinlipidmetabolismenzymesinratepididymalfatafterchroniccentralleptininfusionarerelatedtoalterationsininflammationandinsulinsignaling