ESPE Abstracts (2015) 84 P-1-27

Activation of Insulin Signaling in Gastrocnemius after Central Leptin Infusion is Associated with an Increase in Proliferation and Muscle Fibre Size

Vicente Barriosa,b, Emma Burgos-Ramosa,c, Sandra Canellesa,b, Amaia Rodríguezb,d, Javier Gómez-Ambrosib,d, Julie A Chowena,b, Gema Frühbeckb,d & Jesús Argentea,b

aDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; bCentro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain; cIMDEA Food Institute, Madrid, Spain; dMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain

Background: Skeletal muscle is the largest tissue involved in the insulin-stimulated disposal of glucose, with its size being controlled by hormonal status, among other factors. Leptin plays a primary role in the regulation of glucose homeostasis with a substantial degree of insulin and leptin cross-talk in muscle. However, the relationship between the leptin’s central effects on insulin sensitivity in muscle and associated structural changes remain unclear.

Objective and hypotheses: We hypothesised that chronic central leptin infusion modifies muscle proliferation and fibre size through activation of insulin sensitivity. Thus, we analysed whether the possible changes in insulin signalling and glucose uptake in the gastrocnemius of rats infused with leptin are associated with structural modifications.

Method: 18 male Wistar rats were divided into control (C), intracerebroventricular leptin infusion (12 μg per day) for 14 days (L) and pair-fed (PF) groups. We analyzed serum levels of insulin by ELISA, muscle glucose concentrations by a colorimetric method, insulin signaling by a multiplexed bead immunoassay, as well as glucose transporter 4 (GLUT4) and insulin receptor (IR) levels by Western blot. Proliferating cell nuclear antigen (PCNA) in gastrocnemius was studied by immunohistochemistry and the area of fibers by haematoxylin-eosin staining.

Results: Serum insulin concentrations were unaltered in the PF and L groups. Muscle levels of glucose, GLUT4 and IR were unchanged in PF and augmented in the L group. Phosphorylation of IR substrate-1, Akt and mammalian target of rapamycin (mTOR) were enhanced in L, whereas phosphorylation of phosphatase and tensin homolog (PTEN) was reduced in the same group. The number of PCNA-positive nuclei and area of fibers in the gastrocnemius were also increased in L group.

Conclusion: Central leptin promotes an increase in muscle proliferation and size that could be associated with improved insulin sensitivity.