Diabetes 2013 July-3

Adipose tissue promotes a serum cytokine profile related to lower insulin sensitivity after chronic central leptin infusion

Plos One 2012; 7: e46893

Emma Burgos-Ramos, Sandra Canelles, Arancha Perianes-Cachero, Eduardo Arilla-Ferreiro, Jesús Argente, Vicente Barrios

Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa and Department of Pediatrics, Universidad Autónoma de Madrid, E-28009, Madrid, Spain


BACKGROUND: Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity.

METHODS: We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into 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 the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay.

RESULTS: Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L.

CONCLUSION: Leptin produces a serum inflammatory profile closely correlated with lower insulin sensitivity. Adipose tissue contributes to the generation of this adverse profile and the increased synthesis of cytokines seems to be related with the activation of leptin signaling and independent of insulin resistance.

IMPACT: Pharmacological inhibition of leptin signaling in adipose tissue could be of interest for reducing the low grade inflammatory state associated to obesity.


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