Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: (a) MALDI-TOF spectra of reaction mixture. The ratio denotes the molar ratio of leptin monomer to polymer. (b) SEC of leptin conjugates eluted from Superdex75 100/300 GL column in 10% MeOH/0.25 M sodium phosphate, pH 7.5 at 0.5 ml/min. (c) SDS-PAGE of pooled fractions in SEC denoted by elution time. Fraction of 20.3–21.9 min in LepNP85 and fraction of 18.5–21 min in LepNPEG5K were used.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Polymer, SDS Page

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: SDS-PAGE of the reaction mixture of leptin and Leptin-2PCA with CHO-P85-OH or with P85-DSP.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: SDS Page

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: (a) Leptin 1:1 physical mixture with P85 or PEG5K. (b) Leptin 1:1 conjugates.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques:

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: Leptin and leptin 1:1 conjugates were eluted from Jupiter C4 column (particle diameter 5 μm, pore diameter 300 Å, 4.6 × 100 mm) by gradient elution at 1 ml/min and 25 °C, and monitored by absorption at 220 nm. Mobile phase A: water + 0.1% TFA; mobile phase B: acetonitrile + 0.1% TFA: isopropanol 50:50 (v/v). The elution started from 5% B for 5 min, then linearly increased to 95% B at 1%/min, and stayed at 95% B till 100 min.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques:

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: (a) Representative sensorgram for native leptin. (b) Representative sensorgram for LepNP85 1:1 conjugates. (c) Representative sensorgram for LepDSSP85 1:1 conjugates. (d) Dissociation constants (KD) of leptin and leptin 1:1 conjugates. Data are mean ± SD, n= 5~12. *** p < 0.001 and n.s. not significant by One-way ANOVA and post Newman-Keuls Multiple Comparison Test.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Comparison

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: (a) Dose response of leptin and LepNP85 1:1 conjugates. Data are mean ± SEM, n=3. (b) Comparison of leptin and leptin 1:1 conjugates at 100 ng/mouse. Data are mean ± SEM, n= 5~7. ** p < 0.01 and *** p < 0.001 by One-way ANOVA and post Newman-Keuls Multiple Comparison Test.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Comparison

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: Serum clearance, unidirectional brain influx rates and initial volumes of brain distribution for leptin and leptin 1:1 conjugates.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques:

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: Male CD-1 mice were co-injected with 125I-LepNP85 and 131I-leptin. Data are mean ± SEM, n=7/time point, * p < 0.05, ** p < 0.01, and *** p < 0.001 by Two-way ANOVA.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Injection

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: Each male CD-1 mouse was injected with 125I-labeled LepNP85 with or without 10 μg of cold leptin. Data are mean ± SEM, n=7/time point, * p < 0.05 by Two-way ANOVA.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Injection, Labeling

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Intranasal Delivery of N-terminal Modified Leptin-Pluronic Conjugate for Treatment of Obesity

doi: 10.1016/j.jconrel.2017.03.029

Figure Lengend Snippet: 1 μg of biotin-labeled leptin and LepNP85 in 1 μl of PBS were injected locally into brain by ICV injection. The concentrations of biotin-labeled proteins in brain lysate and plasma were analyzed by ELISA. (a) Blood absorption of biotin-leptin and biotin-LepNP85 after ICV injection. (b) Brain retention of biotin-leptin and biotin-LepNP85 after ICV injection. Data are mean ± SEM, n=4/time point, * p < 0.05 by One-way ANOVA and post Dunnett’s Multiple Comparison Test, and *** p < 0.001 by Two-way ANOVA.

Article Snippet: Recombinant mouse leptin and recombinant human leptin receptor-Fc chimeras were purchased from R&D Systems (Minneapolis, MN).

Techniques: Labeling, Injection, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Comparison

Journal: Indian Journal of Endocrinology and Metabolism

Article Title: Leptin therapy, insulin sensitivity, and glucose homeostasis

doi: 10.4103/2230-8210.105571

Figure Lengend Snippet: Euglycemic hyperinsulinemic clamps of leptin-deficient patients while on leptin and after brief periods of leptin withdrawal (from Paz-Filho et al .). Glucose infusion rates increased in eight out of nine times when leptin therapy was briefly interrupted. The substantial weight gain after leptin withdrawal was responsible for acutely increasing insulin sensitivity

Article Snippet: [ ] Physiological doses of recombinant methionyl human leptin (r-metHuLeptin, Metreleptin ® , Amylin Pharmaceuticals, USA, 0.02-0.04 mg/kg/day) were initiated on the leptin-deficient individuals being assessed by our group at ages 5 (boy), 27 (male), 30 and 40 (females).

Techniques:

Journal: Indian Journal of Endocrinology and Metabolism

Article Title: Leptin therapy, insulin sensitivity, and glucose homeostasis

doi: 10.4103/2230-8210.105571

Figure Lengend Snippet: Interactions between fat, brain, pancreas and bone. Leptin activates the sympathetic tonus, which inhibits insulin secretion and stimulates Esp expression in the osteoblast (via stimulation of the adrenergic beta 2 receptor). Esp inhibits osteocalcin, decreasing insulin expression. Leptin inhibits pancreatic insulin. Insulin, in turn, stimulates leptin expression in the white adipose tissue. Adapted from Kieffer and Habener. H: Hypothalamus

Article Snippet: [ ] Physiological doses of recombinant methionyl human leptin (r-metHuLeptin, Metreleptin ® , Amylin Pharmaceuticals, USA, 0.02-0.04 mg/kg/day) were initiated on the leptin-deficient individuals being assessed by our group at ages 5 (boy), 27 (male), 30 and 40 (females).

Techniques: Expressing