title: Regulation of insulin-stimulated glucose uptake in rat white adipose tissue upon chronic central leptin infusion: effects on adiposity.
abstract: Leptin enhances the glucose utilization in most insulin target tissues and paradoxically decreases it in white adipose tissue (WAT), but knowledge of the mechanisms underlying the inhibitory effect of central leptin on the insulin-dependent glucose uptake in WAT is limited. After 7 d intracerebroventricular leptin treatment (0.2 μg/d) of rats, the overall insulin sensitivity and the responsiveness of WAT after acute in vivo insulin administration were analyzed. We also performed unilateral WAT denervation to clarify the role of the autonomic nervous system in leptin effects on the insulin-stimulated [(3)H]-2-deoxyglucose transport in WAT. Central leptin improved the overall insulin sensitivity but decreased the in vivo insulin action in WAT, including insulin receptor autophosphorylation, insulin receptor substrate-1 tyrosine-phosphorylation, and Akt activation. In this tissue, insulin receptor substrate-1 and glucose transporter 4 mRNA and protein levels were down-regulated after central leptin treatment. Additionally, a remarkable up-regulation of resistin, together with an augmented expression of suppressor of cytokine signaling 3 in WAT, was also observed in leptin-treated rats. As a result, the insulin-stimulated glucose transporter 4 insertion at the plasma membrane and the glucose uptake in WAT were impaired in leptin-treated rats. Finally, denervation of WAT abolished the inhibitory effect of central leptin on glucose transport and decreased suppressor of cytokine signaling 3 and resistin levels in this tissue, suggesting that resistin, in an autocrine/paracrine manner, might be a mediator of central leptin antagonism of insulin action in WAT. We conclude that central leptin, inhibiting the insulin-stimulated glucose uptake in WAT, may regulate glucose availability for triacylglyceride formation and accumulation in this tissue, thereby contributing to the control of adiposity.
authors.affiliation: Area de Bioquímica, Facultad de Químicas, Regional Centre for Biomedical Research, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Bonzón-Kulichenko
authors.forename: Teresa
authors.initials: T
authors.lastname: Fernández-Agulló
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moltó
authors.forename: Rosario
authors.initials: R
authors.lastname: Serrano
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Ros
authors.forename: José M
authors.initials: JM
authors.lastname: Carrascosa
authors.forename: Carmen
authors.initials: C
authors.lastname: Arribas
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Antonio
authors.initials: A
authors.lastname: Andrés
authors.forename: Nilda
authors.initials: N
authors.lastname: Gallardo
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D001692:Biological Transport / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin; D020738:Leptin; D005947:Glucose