General characteristics of experimental animals. A.

<p>Mean daily food intake in rats that received saline (C) or chronic leptin (L) and the pair-fed group (PF). <b>B.</b> Mean body weight measurements throughout the study in the same groups. <b>C.</b> Epididymal fat content in the same groups. <b>D.</b> Serum leptin concentrations in the same groups. <b>E.</b> Serum glucose concentrations in the same groups. <b>F.</b> Serum insulin concentrations in the same groups. NS, non-significant; *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.01 by ANOVA. * in panels A and B indicates significant difference (<i>p</i><0.05) between C and L or PF groups, whereas ^# indicates significant difference (<i>p</i><0.05) between PF and L groups.</p

Relative mRNA and protein content of cytokines in subcutaneous adipose tissue. A.

<p>Relative mRNA levels of interleukin-2 (IL-2) in inguinal fat of rats that received saline (C) or chronic leptin (L) and pair-fed group (PF). <b>B.</b> Protein content of IL-2 in the same groups. <b>C.</b> Relative mRNA levels of interferon-γ (IFN-γ) in the same groups. <b>D.</b> Protein content of IFN-γ in the same groups. <b>E.</b> Relative mRNA levels of tumor necrosis factor α (TNF-α) in the same groups. <b>F.</b> Protein content of TNF-α in the same groups. NS, non-significant; *<i>p</i><0.05 by ANOVA.</p

Relative mRNA and protein content of cytokines in visceral adipose tissue. A.

<p>Relative mRNA levels of interleukin-2 (IL-2) in epididymal fat of rats that received saline (C) or chronic leptin (L) and the pair-fed group (PF). <b>B.</b> Protein content of IL-2 in the same groups. <b>C.</b> Relative mRNA levels of interferon-γ (IFN-γ) in the same groups. <b>D.</b> Protein content of IFN-γ in the same groups. <b>E.</b> Relative mRNA levels of tumor necrosis factor α (TNF-α) in the same groups. <b>F.</b> Protein content of TNF-α in the same groups. NS, non-significant; *<i>p</i><0.05, ***<i>p</i><0.001 by ANOVA.</p

Linear correlations of homeostasis model assessment of insulin resistance (HOMA-IR), Δ glycemia ([glycemia after 120 min of insulin bolus] – [glycemia before insulin bolus]) after intracerebroventricular insulin infusion (ICVII) and area under the curve (AUC) after intraperitoneal insulin tolerance test (IPITT) with serum levels of leptin, interleukin (IL)-2 and IL-4.

<p>r, correlation coefficient; NS, non-significant; *<i>p</i><0.05, **<i>p</i><0.01.</p

Insulin signaling in subcutaneous and visceral fat. A.

<p>Relative levels of the insulin receptor beta chain (IRβ) in inguinal fat of rats that received saline (C) or chronic leptin (L) and the pair-fed group (PF). <b>B.</b> Relative IRβ levels in epididymal fat of the same groups. <b>C.</b> Relative phosphorylated (p) Akt on serine 473 (pSer473-Akt) protein levels in inguinal fat of the same groups. <b>D.</b> Relative pSer473-Akt protein levels in epididymal fat of the same groups. <b>E.</b> Relative levels of the forkhead box-containing protein O-1 (FOXO1) in inguinal fat of the same groups. <b>F.</b> Relative FOXO1 levels in epididymal fat of the same groups. <b>G.</b> Relative levels of the protein tyrosine phosphatase 1B (PTP1B) in inguinal fat of the same groups. <b>H.</b> Relative PTP1B levels in epididymal fat of the same groups. The data are expressed as a percentage of the control ratio. DU, densitometry units; NS, non-significant; *<i>p</i><0.05 by ANOVA, ***<i>p</i><0.001 by ANOVA.</p

Homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity as delta (Δ) in glycemia after intracerebroventricular insulin infusion (ICVII) and glycemia during an intraperitoneal insulin tolerance test (IPITT). A.

<p>HOMA-IR index in rats that received saline (C) or chronic leptin (L) and pair-fed group (PF). <b>B.</b> Delta (Δ) in glycemia ([glycemia after 120 min of insulin bolus] – [glycemia before insulin bolus]) in rats that received saline plus acute insulin (insulin, C+I), chronic leptin plus acute insulin (L+I) and the pair-fed group plus insulin (PF+I). <b>C.</b> Serum glucose levels before (0 min) and during (30, 60, 90 and 120 min) an IPITT. *<i>p</i><0.05, **<i>p</i><0.01 by ANOVA.</p

Serum levels of cytokines. A.

<p>Serum interleukin (IL)-2 levels in rats that received saline (C) or chronic leptin (L) and the pair-fed group (PF). <b>B.</b> Serum IL-4 levels in the same groups. <b>C.</b> Serum IL-6 levels in the same groups. <b>D.</b> Serum IL-10 levels in the same groups. <b>E.</b> Serum interferon γ (IFN-γ) levels in the same groups. <b>F.</b> Serum tumor necrosis α (TNF-α) levels in the same groups. NS, non-significant; *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 by ANOVA.</p

Serum cytokine levels (pg/ml), insulin resistance or sensitivity indexes, relative mRNA levels and concentration of cytokines in subcutaneous and visceral adipose tissue (pg/mg of protein) and intracellular signaling (expressed as % control) in both fat depots.

<p>FOXO1, forkhead box O number 1; HOMA-IR, homeostasis model assessment of insulin resistance; IL, interleukin; IFN-γ, interferon-γ; IR, insulin receptor; ObRb, long form of leptin receptor; p/t, phosphorylated/total; PTP1B, protein tyrosine phosphatase 1B; SOCS3, suppressor of cytokine signaling 3; STAT3, transducer and activator of transcription factor 3; TNF-α, tumor necrosis factor α. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 by ANOVA vs. control; ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001 by ANOVA vs. pair-fed group.</p

Correlation analyses between plasma concentrations of BDNF, IGF-1 and IGFBP-3 and age in abstinent cocaine users (black circles) and control subjects (white circles).

<p><b>A)</b> BDNF (pg/mL); <b>B)</b> IGF-1 (ng/mL); and <b>C)</b> IGFBP-3 (μg/mL). Dots are individual values. (r) Pearson´s correlation coefficient; (rho) Spearman´s correlation coefficient; (p) p-value for statistical significance.</p

Plasma concentrations of BDNF, IGF-1 and IGFBP-3 according to sex in abstinent cocaine users and control subjects.

<p><b>A)</b> BDNF (pg/mL); <b>B)</b> IGF-1 (ng/mL); and <b>C)</b> IGFBP-3 (μg/mL). Bars are the means and SD. Data were analyzed by two-way analyses (cocaine use [cocaine group and control group] and sex [women and men]).</p