Endocrine Abstracts (2017) 49 EP655 | DOI: 10.1530/endoabs.49.EP655

Insulin signaling is involved in the regulation of UCP-1 expression in brown adipose tissue after chronic central leptin infusion

Vicente Barrios1, Laura M. Frago1, Sandra Canelles1, Emma Burgos-Ramos2, Julie A. Chowen1 & Jesús Argente1

1Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa and CIBERobn, Instituto de Salud Carlos III, Madrid, Spain; 2Facultad de Ciencias Ambientales y Bioquímica, Universidad Castilla-la Mancha, Toledo, Spain.

Background: Brown adipose tissue (BAT) plays a pivotal role in the regulation of energy homeostasis and thermogenesis. This tissue responds to insulin, favoring the expression of uncoupling protein-1 (UCP-1), that in turn is inhibited by insulin-desensitizing cytokines. Leptin may abolish some of the effects of fasting on these parameters through its cross-talk with insulin-related signaling targets.

Objectives: We hypothesized that leptin infusion prevents UCP-1 depletion induced by food restriction through activation of insulin signaling in brown adipose tissue.

Methods: We studied 18 male Wistar rats divided into three groups: rats receiving saline icv (controls, C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by L. We analyzed relative mRNA levels of UCP-1 and glucose transporter 4 (GLUT4) by real time-PCR and changes in the cytokine levels and activation of insulin-related signaling targets by multiplexed bead immunoassay.

Results: Relative UCP-1 mRNA levels were reduced in PF and unchanged in the L group. The mRNA levels of GLUT4 were increased in L rats, as well phosphorylation of insulin receptor substrate 1. Akt phosphorylation on threonine 308 was reduced in PF and increased in L. Among the studied cytokines, fractalkine and TNF-α were decreased in the L group, with no changes in PF rats.

Conclusion: Central leptin infusion could preserve UCP-1 expression in brown adipose tissue through activation of insulin-related signaling.

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