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

Author:

Casado María E.12,Canelles Sandra12,Arilla-Ferreiro Eduardo3,Frago Laura M.124ORCID,Barrios Vicente12ORCID

Affiliation:

1. Department of Endocrinology, Instituto de Investigación La Princesa, Hospital Infantil Universitario Niño Jesús, E-28009 Madrid, Spain

2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain

3. Department of Biological Systems, Faculty of Medicine, Universidad de Alcalá, E-28871 Alcala de Henares, Spain

4. Department of Pediatrics, Faculty of Medicine, Universidad Autónoma de Madrid, E-28029 Madrid, Spain

Abstract

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.

Funder

Ministerio de Ciencia e Innovación

Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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