recombinant mouse leptin  (R&D Systems)

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a, Schematic of the combined Xenium spatial transcriptomics and pSTAT3 immunofluorescence workflow used to quantify leptin signaling across hypothalamic cell types in chow-fed and diet-induced obese (DIO) mice. b , UMAP embedding of neurons (17 populations; n=6 mice total) across all spatially profiled sections, colored by transcriptionally defined Lepr cell clusters. c , Marker gene expression across Lepr neuron subtypes, highlighting canonical cell type markers. d , UMAP embedding showing pSTAT3-positive Lepr neurons (green). e, Numbers of pSTAT3-positive cells across Lepr neuron subtypes in chow-fed and HFD-fed mice (n=3 mice per group; 2–3 sections per mouse). DIO increased pSTAT3 positivity nearly 10-fold overall (4.45±0.65% vs. 0.47±0.2%, P <0.001; generalized linear mixed-effects model with binomial distribution, animal as random effect). This was driven predominantly by Lepr/Glp1r neurons, which showed a >20-fold increase (21.1±1.1% vs. 0.33±0.2%, P <1×10⁻¹⁰) and accounted for >60% of all pSTAT3-positive Lepr neurons in DIO. P -values adjusted by Benjamini-Hochberg. f , Representative distribution of the each population of Lepr neurons across a single coronal section, color-coded as in b, c. Right panels show representative Xenium and immunofluorescence images showing spatial colocalization of Lepr, Glp1r, Trh , and pSTAT3 in the boxed areas of the larger panel. g , DIO-induced transcriptional changes in Lepr/Glp1r neurons, including increased expression of canonical leptin target genes ( Socs3, Nlrc5, Sbno2, Atf3; red) and immediate-early genes (e.g., Junb, Vgf ), indicating robust and sustained leptin signaling.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Spatial Transcriptomics, Immunofluorescence, Marker, Gene Expression, Expressing

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Experimental design for snRNA-seq profiling of hypothalamic neurons across metabolic states: chow-fed (Chow; n=7), overnight-fasted (Fasting; n=3), fasted and refed (90 min) (Refeed; n=4), and DIO mice (HFD; n=8). b , UMAP embedding of MBH neurons (>40,000 nuclei; mean 12,401 transcripts per nucleus), with Lepr -expressing neurons labelled by subtype. c , Effects of nutritional manipulations on the total transcriptome of each neuronal population. Expression distance estimate in response to fasting (x-axis) and DIO (y-axis). Data for Lepr neurons is highlighted in cell-type specific colors. Solid diagonal line indicates matched effects between perturbations. d , Leptin gene signature (LGS) expression in for each nutritional manipulations across the indicated subsets of Lepr neurons; HFD (red), refeed (light green), chow (yellow), fasting (dark green)). e , Hierarchical clustering and grouping of differentially expressed genes identified in Lepr/Glp1r neurons. Neuronal activity genes and GABA receptor subunits highlighted.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Expressing, Activity Assay

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a,b , UMAP embedding of mediobasal hypothalamic neurons colored by individual mouse (a) and sequencing batch (b). c , Distribution of UMI counts (top) and genes detected (bottom) per cell across all samples (chow n=7, DIO n=8, fasted n=3, refed n=4). d , UMAP colored by predicted Campbell neuron subtype. e , Mapping confidence scores, with highest confidence in the Lepr/Glp1r population. f , Proportion of cells assigned to each neuronal cluster (n01-n34) across individual samples, showing consistent cluster composition across mice and conditions. g , MINT sPLS-DA projection of three independent leptin treatment transcriptomic datasets used to derive the leptin gene signature (LGS). Fasted/control (blue) and leptin-treated (orange) samples separate along the first two components. h , Gene ontology enrichment of LGS genes, highlighting response to peptide hormone and JAK-STAT signaling among the top terms. i , Model weights for individual LGS genes. j , LGS expression across nutritional states in Tbx19 and Irx3 neurons (***P<0.001). k , Correlation between fasting-induced (y-axis) and DIO-induced (x-axis) log₂ fold changes in AgRP, Lepr/Glp1r, and POMC neurons.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Sequencing, Control, Expressing

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Experimental design of wild-type (WT) mice treated with 3 mg/kg of leptin of saline and sacrificed 1, 3, 6, or 24 hours after injection. MBH nuclei were collected for snRNA-seq. b, Transcriptional distance between cells from leptin treated and control mice. c, LGS changes across Lepr/Glp1r , Pomc and Agrp neurons . d, Overlap between genes induced by acute leptin treatment and those upregulated in DIO in Lepr/Glp1r neurons (93 shared genes; odds ratio=185.3, P =6.28×10⁻²⁴, Fisher’s exact test), indicating that direct leptin action recapitulates a substantial portion of the DIO transcriptional program.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Saline, Injection, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a-c , UMAP embedding of mediobasal hypothalamic neurons from lean mice treated with leptin (3 mg/kg) or saline and harvested at 1, 3, 6, or 24 hours post-injection (n=4-6 per timepoint per group), colored by treatment (a), hours post-injection (b), and sequencing batch (c). d , UMAP colored by neuronal cell type identity, with key Lepr-expressing populations labeled. e , Number of differentially expressed genes (leptin vs saline; adjusted P<0.05) per neuronal population. Red, upregulated; blue, downregulated. f , Volcano plot of leptin-induced differential expression in Lepr/Glp1r neurons. Highlighted genes include canonical leptin targets (blue), immediate early/neuronal activity genes (red), and GABA receptor subunits (green). Dashed line, adjusted P =0.05.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Saline, Injection, Sequencing, Expressing, Labeling, Quantitative Proteomics, Activity Assay

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Lepr/Glp1r neurons constitute ∼78% of all Lepr-expressing GABAergic (Gad1+) input to AgRP (Npy+) neurons, based on reanalysis of published rabies-traced AgRP neuron afferents. Feature plots show expression of Gad1, Glp1r, Npy, and Lepr across traced populations; circled clusters indicate the Lepr/Glp1r population. b,c , UMAP embedding of mediobasal hypothalamic neurons from Glp1r Lepr KO and control mice (35,538 nuclei total), colored by genotype (b) and diet (c) (chow vs DIO; n=6-7 per group). d , UMAP colored by predicted cell type identity (41 clusters) based on label transfer from the nutritional perturbation reference atlas. e , Change in leptin gene signature (LGS) expression in Glp1r Lepr KO relative to control mice across Lepr neuron subtypes (open circles denote P <0.05; linear mixed-effects model).

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Expressing, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Schematic of retrograde rabies tracing from ARC Npy neurons in Lepr Cre-sun1Gfp ;Npy Flp mice. Starter cells (ARC) express TVA and rabies-G via Npy Flp ; rabies-labeled cells are magenta, Lepr -expressing cells green, and co-labeled cells ( Lepr -expressing afferents) show both signals. b, c, Representative images of tissue sections from experiments as in (a). *Indicates viral hit site. Afferent DMH Lepr cells indicated by white arrows. d , Schematic of retrograde rabies tracing from Agrp neurons in Agrp Cre; Glp1r Flp-TDT mice. Rabies-labeled cells are green, Glp1r -expressing cells red, and co-labeled cells ( Glp1r -expressing afferents) show both signals. e, f , Representative images of tissue sections from experiments as in (d); *indicates viral hit site. Rabies-labeled Glp1r afferent cells indicated with white arrows. Scale bars: 200 µm (main images), 100 µm (insets). g , h , Experimental paradigm: Lepr was ablated in Glp1r expressing neurons and animals were fed chow diet ( Agrp , n=7; Glp1r , n=6 Lepr KO and n=6 control) and either sacrificed at 4-5 weeks of age switched onto a HFD for 15 weeks ( Agrp n=2; Glp1r , n=7 Lepr KO and n=6 control) until sacrifice. Mediobasal hypothalami were collected for snRNA-seq. i, Leptin gene signature (LGS) expression in Lepr/Glp1r neurons from for lean (Chow) or DIO Lepr Glp1r KO and control (WT) mice. LGS was significantly reduced in KO neurons (β=−0.087, P <1.0×10⁻⁹; linear mixed-effects model), with a significant genotype × diet interaction ( P =2×10⁻⁹). j, PCA projection of Lepr/Glp1r neurons from DIO Lepr Glp1r KO (red) and Control (blue) mice onto the nutritional perturbation embedding. Centroids for DIO (orange) and fasted (teal) conditions shown as large circles. Lepr Glp1r KO neurons cluster with fasted wild-type neurons (PC1 permutation test, P=0.001), indicating LepR signaling is required to adopt the DIO transcriptional state. k, Volcano plot of differentially expressed genes in Lepr/Glp1r neurons (KO versus WT, DIO). Loss of Lepr abolished the DIO-associated induction of immediate early genes ( Fos , log₂FC=−2.14, adj. P =0.018; Vgf , log₂FC=−1.76, adj. P =1.3×10⁻⁴; Homer1 , log₂FC=−0.66, adj. P =0.027) and reversed the downregulation of GABA receptor subunits ( Gabra3, Gabra4, Gabra5, Gabrb1–b3 ). Dashed line, adjusted P =0.05. See Supplementary Table 7 for full results. l, PCA projection of Agrp neurons from DIO Lepr Glp1r KO (red) and Control (blue) mice; centroids for DIO (orange) and fasted (teal) conditions shown as large circles, as in ( j ). Agrp neurons shift toward the fasted transcriptional state in Lepr Glp1r KO mice (PC1 permutation test, P=0.001), indicating propagation of the transcriptional effect from Lepr/Glp1r neurons. m, Volcano plot of differentially expressed genes in Agrp neurons (KO versus WT, DIO; 128 genes). Genes colored by their response to fasting: orange, fasting-upregulated; blue, fasting-downregulated; grey, neither. Fasting-upregulated genes were enriched among genes increased in KO (OR=8.56, P =1.05×10⁻⁸, Fisher’s exact test), and fasting-downregulated genes were enriched among decreased genes (OR=22.67, P =6.76×10⁻¹⁹), confirming a fasting-like transcriptional state despite obesity.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Labeling, Expressing, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Schematic and representative histology of bilateral AAV-FLEX-FREX-hM3Dq injection into the caudal ARC/ventral DMH of Glp1r-ires-Cre;Trh-p2a-Dre mice. Scale bar: 200 µm. b , Spatial transcriptomics reference map showing the Lepr/Glp1r neuron population (red) targeted by the intersectional DREADD strategy. c , Summary of the DREADD cohort (main text ). d , Baseline characteristics of chow-fed Glp1r Lepr KO (n=20) and control (n=14) mice used for leptin-dependent feeding suppression experiments (main text ). e , Baseline chow-period body weight and DEXA body composition of Glp1r Lepr KO (n=9) and control (n=10) mice prior to HFD exposure . Data are mean ± SD.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Injection, Spatial Transcriptomics, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: Mice containing activating DREADDs in Glp1r/Trh neurons were treated with saline or CNO at the onset of the dark cycle (a), during refeeding following an overnight fast (b), or prior to ghrelin treatment (c). a , Cumulative dark-cycle food intake at 0, 1, 2, and 3 hours following IP CNO or saline in a within-subject crossover design (n=5).. b , Cumulative post-fast food intake at 0, 1, 2, 4, 6, and 8 hours following IP CNO or saline (n=5). c , Cumulative food intake following IP ghrelin with CNO or saline pre-treatment at 0, 1, 2, 4, 6, and 8 hours (n=4). d, Effect of leptin (dark teal) versus saline (light teal) pre-treatment on ghrelin-induced 24-hour food intake in lean Lepr Glp1r KO (KO) and control (WT) mice. Lines connect within-subject measurements (crossover design). e, Cumulative post-fast food intake following leptin (dark teal) or saline (light teal) administration in WT (left) and KO (right) mice. f, g , Body weight (f) and daily food intake (g) before and 7 days after HFD exposure in Lepr Glp1r KO (n=9) and Control (n=10) mice. h , Food intake from (g) separated by dark (top) and light (bottom) cycle. The excess intake in Lepr Glp1r KO mice was concentrated in the dark cycle (genotype × time: χ²(9)=38.33, P =1.52×10⁻⁵). Dashed line indicates HFD switch. All panels: * P <0.05, **P<0.01, ***P<0.001. A-c, e-h: Plotted points represent mean values. Error bars (a-c) and shaded regions (e-h) denote SEM.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Saline, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a,b, Baseline characteristics of Glp1r Lepr KO and control mice used in the chow vs DIO fasting-refeeding experiment (main text ). Chow-fed and DIO cohorts are independent groups of animals. c-e, Baseline characteristics of DIO Glp1r Lepr KO (n=12) and control (n=11) mice used in the ghrelin feeding experiment. c , Summary table including plasma leptin for a subset of mice (KO n=4, WT n=3). d , Individual body weights and ( e ) plasma leptin by genotype, confirming hyperleptinemia in both genotypes. Data are mean ± SD (tables) or mean ± SEM (dot plots) with individual animals shown.

Article Snippet: Mouse recombinant leptin (R&D Systems, #498-OB) was reconstituted to 1 mg/ml in 20 mM Tris-HCl pH 8.0 (Invitrogen, #10434742).

Techniques: Control, Clinical Proteomics

Journal: bioRxiv

Article Title: Epigenetic Silencing of Carotid Body TRPM7 Attenuates Hypertension in Obese Mice

doi: 10.64898/2026.03.05.709322

Figure Lengend Snippet: (A ) (i) Representative integrated CSN activity trace in a CB preparation from an MO-CTL-treated mouse; showing the sequential effects of leptin and a TRPM7 blocker FTY720 during normoxia and hypoxia. Raw tracings throughout the time course (X-axis) are shown at the top; the scale bars represent 2 min. (ii) Summary data showing leptin induced significant increase in basal CSN activity (P = 0.004), which was abolished by Trpm7 receptor inhibitor FTY 720 (P = 0.005; N=5). (iii) Summary data showing CB chemosensitivity Hx (hypoxia) – Nx (normoxia), which was markedly enhanced by leptin (P = 0.002) and reversed by FTY 720 (P = 0.002; N=5). ( B) . (iv) Representative integrated CSN activity in a preparation from an MO-R1 treated mouse showing the sequential effects of leptin and a TRPM7 blocker FTY720 during normoxia and hypoxia. Raw tracings throughout the time course (X-axis) are shown at the top; the scale bars represent 2 min. (v) Summary data of CSN activity under normoxia, which did not significantly increase by leptin (P = 0.065; N=5) and was unaffected by FTY 720 (P = 0.065; N = 5). (iv) Summary data showing CB chemosensitivity responses (Hx − Nx) remained unchanged across treatments (P = 0.451; N= 5). Values are expressed as box and whisker plots (median, 25-75% centiles and minimum and maximum values; mean ± S.D.). Data were statistically compared by one-way repeated measures ANOVA with Holm-Sidak post-hoc comparisons. P< 0.05 was considered significant.

Article Snippet: Leptin (Cat. #498-OB; R&D Systems, Minneapolis, MN, USA), FTY720 (Cat. #SML0700; Sigma-Aldrich, St. Louis, MO, USA), and isoflurane (Item #502017; MWI Animal Health, AmerisourceBergen; Boise, ID, USA) were used in all experimental protocols.

Techniques: Activity Assay, Whisker Assay

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: r‐Leptin and Fc‐Leptin characterization. (A) Comparison of r‐Leptin and Fc‐Leptin in vitro pSTAT3 functional activity with the human long‐form leptin receptor ( n = 2–4 independent experiments). (B) Comparison of r‐Leptin (10 mg/kg) and Fc‐Leptin (2 mg/kg) plasma exposure following a single SC dose administration in wildtype mice ( n = 3 mice per group). (C) Modelling of differences in pulsatile exposure following dosing with r‐Leptin (10 mg/kg SC BID) versus Fc‐Leptin (single 2 mg/kg dose). (D) Bodyweight in non‐obese mice treated with r‐Leptin 2 mg/kg ( n = 10 mice per group). Comparison shown is between vehicle and r‐Leptin at day 6. **** p < 0.0001, DF = 18, t ratio = −9.13. (E) Cumulative food intake (6 days) in non‐obese mice treated with r‐Leptin 2 mg/kg ( n = 10 mice per group). ** p < 0.01, DF = 17.8, t ratio = 3.07. (F) Body weight after a single Fc‐Leptin dose of 20 mg/kg in non‐obese mice ( n = 5 mice per group). Comparison shown is between vehicle and Fc‐Leptin each day. * p < 0.05, ** p < 0.01, DF = 8, t ratio = −3.85. (G) Cumulative food intake (6 days) in non‐obese mice that received a single Fc‐Leptin dose of 20 mg/kg ( n = 5 mice per group). *** p < 0.001, DF = 7.01, t ratio = 5.64. Values are shown as mean ± SEM.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Comparison, In Vitro, Functional Assay, Activity Assay, Clinical Proteomics

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: Leptin treatment after weight loss stabilization does not prevent weight regain. (A) Schematic representation of the 10% weight loss/weight maintenance model with a stabilization period in DIO mice fed a 60% HFD. (B) Plasma leptin concentration at baseline and after 21 days of 10% weight loss stabilization ( n = 5 mice per group). Mean plasma leptin concentration (nM) for each group is shown in parenthesis. ** p < 0.01, DF = 6.23, t ratio = 3.77. (C) Body composition at baseline and after 21 days of 10% weight loss stabilization ( n = 40 mice per group). * p < 0.05, **** p < 0.0001, DF = 3, f ratio = 238.7. (D) Body weight and (E) percent body weight change from baseline in DIO mice treated with vehicle, 2 mg/kg r‐Leptin, 20 mg/kg Fc‐Leptin, or 0.05 mg/kg Liraglutide ( n = 10 mice per group). Comparisons shown are between vehicle and liraglutide on day 39. ** p < 0.01, **** p < 0.0001, DF = 36, t ratio = −9.15. (F) Cumulative food intake (days 25 to 40) in DIO mice with treated with vehicle, 2 mg/kg r‐Leptin, 20 mg/kg Fc‐Leptin, or 0.05 mg/kg Liraglutide ( n = 5–10 mice per group). * p < 0.05, ** p < 0.01, DF = 3, f ratio = 4.89. (G) Body weight and (H) percent body weight change from baseline in DIO mice treated with pharmacological (2 mg/kg) and non‐pharmacological (0.2 and 0.02 mg/kg) doses of r‐Leptin or 0.05 mg/kg of Liraglutide ( n = 10 mice per group). Comparisons shown are between vehicle and liraglutide on day 44. ** p < 0.01, **** p < 0.0001, DF = 45, t ratio = −7.74. (I) Cumulative food intake (days 25 to 45) in DIO mice with treated with pharmacological (2 mg/kg) and non‐pharmacological (0.2 and 0.02 mg/kg) doses of r‐Leptin or 0.05 mg/kg of Liraglutide ( n = 10 mice per group). * p < 0.05, ** p < 0.01, DF = 4, f ratio = 5.25. (J) Fat mass and (K) lean mass of DIO mice treated with vehicle, 2 mg/kg r‐Leptin, or 0.05 mg/kg Liraglutide at the end of the weight maintenance phase ( n = 10 mice per group). *** p < 0.001, DF = 2, f ratio = 12.15. Values are shown as mean ± SEM. DIO, diet‐induced obesity; CR, caloric restriction; Wt, weight.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: Leptin treatment does not prevent weight regain after 10% weight loss and 30% lowering of circulating leptin. (A) Schematic representation of the 10% weight loss/weight maintenance model in DIO mice fed 60% HFD. (B) Plasma leptin concentration at baseline and after 10% weight loss ( n = 5 mice per group). Mean plasma leptin concentration (nM) for each group is shown in parenthesis. ** p < 0.01, DF = 7.9, t ratio = 4.47. (C) Body composition at baseline and after 10% weight loss ( n = 30 mice per group). *** p < 0.001, **** p < 0.0001, DF = 3, f ratio = 207.8. (D) Body weight and (E) percent body weight change from baseline in DIO mice treated with 2 mg/kg r‐Leptin after 10% weight loss ( n = 9–10 mice per group). Comparison shown is between vehicle and r‐Leptin at day 14. * p < 0.05, DF = 17, t ratio = −2.12. (F) Cumulative food intake (days 3 to 14) in DIO mice with treated with 2 mg/kg r‐Leptin after 10% weight loss ( n = 9–10 mice per group). (G) Body weight and (H) percent of body weight change from baseline in DIO mice treated with 2 mg/kg Fc‐Leptin after 10% weight loss ( n = 10 mice per group). (I) Cumulative food intake (days 3 to 11) in DIO mice with treated with 2 mg/kg Fc‐Leptin after 10% weight loss ( n = 10 mice per group). Values are shown as mean ± SEM. DIO, diet‐induced obesity; CR, caloric restriction; Wt, weight.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Clinical Proteomics, Concentration Assay, Comparison

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: Continuous high CNS leptin exposure does not prevent weight regain. (A) Schematic representation of the 10% weight loss/weight maintenance model induced by ICV and Alzet pump surgery in non‐obese or DIO mice fed a 60% HFD. (B) Body weight and (C) percent body weight change from baseline in non‐obese mice with continuous ICV aCSF or 8 nM infused r‐Leptin after 10% weight loss ( n = 10 mice per group). Comparisons shown are between aCSF and r‐Leptin (8 nM infused into CSF) on day 23. ** p < 0.01, **** p < 0.0001, DF = 18, t ratio = 5.35. (D) Cumulative food intake (days 4 to 23) in non‐obese mice with continuous ICV aCSF or 8 nM infused r‐Leptin after 10% weight loss ( n = 10 mice per group). ** p < 0.01, DF = 17.8, t ratio = 3.14. (E) Body weight and (F) percent body weight change from baseline in DIO mice with continuous ICV aCSF or r‐Leptin treatment (870 pM or 35 nM infused into CSF) after 10% weight loss ( n = 14 mice per group). (G) Cumulative food intake (days 4 to 23) in DIO mice with continuous ICV aCSF or r‐Leptin (870 pM or 35 nM infused into CSF) treatment after 10% weight loss ( n = 14 mice per group). (H) Plasma leptin concentration in DIO mice after 21 days of ICV aCSF or r‐Leptin infused into CSF ( n = 13–15 mice per group). Mean plasma leptin concentration (nM) for each group is shown in parenthesis. Values are shown as mean ± SEM. ICV, intracerebroventricular; aCSF, artificial cerebrospinal fluid; Wt, weight.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: Leptin treatment does not prevent weight regain when circulating leptin is decreased to match non‐obese mice. (A) Schematic representation of the 20% weight loss/weight maintenance model in DIO mice fed a 60% HFD. (B) Plasma leptin concentration in DIO mice fed a 60% HFD at baseline and after 20% weight loss ( n = 15 mice per group). Mean plasma leptin concentration (nM) for each group is shown in parenthesis. **** p < 0.0001, DF = 18.4, t ratio = 9.43. (C) Body composition of DIO mice fed a 60% HFD at baseline and after 20% weight loss ( n = 15 mice per group). *** p < 0.001, **** p < 0.0001, DF = 3, f ratio = 141.3. (D) Body weight and (E) percent body weight change from baseline in DIO mice treated with vehicle or 2 mg/kg r‐Leptin after 20% weight loss ( n = 11 mice per group). (F) Cumulative food intake (days 43 to 46) during the weight maintenance phase in DIO mice treated with vehicle or 2 mg/kg r‐Leptin after 20% weight loss ( n = 5 mice per group). (G) Schematic representation of the 10% weight loss/weight maintenance model in DIO mice fed a 30% fat diet. (H) Plasma leptin concentration in DIO mice fed a 30% fat diet at baseline and after 10% weight loss ( n = 10 mice per group). Mean plasma leptin concentration (nM) for each group is shown in parenthesis. *** p < 0.001, DF = 18, t ratio = 4.05. (I) Body composition of DIO mice fed a 30% fat diet at baseline and after 10% weight loss ( n = 20 animals per group). **** p < 0.0001, DF = 3, f ratio = 320.8. (J) Body weight and (K) percent body weight change from baseline in DIO mice treated vehicle or 2 mg/kg Fc‐Leptin after 10% weight loss ( n = 10 mice per group). (L) Cumulative food intake (days 7 to 20) during the weight maintenance phase in DIO mice treated with vehicle or 2 mg/kg Fc‐Leptin after 10% weight loss ( n = 10 mice per group). Values are shown as mean ± SEM. CR, caloric restriction; DIO, diet‐induced obesity; Wt, weight.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Diabetes, Obesity & Metabolism

Article Title: Evaluation of leptin treatment on maintenance of body weight loss in diet‐induced obese mice

doi: 10.1111/dom.70207

Figure Lengend Snippet: Summary of the relationship between fat mass, leptin exposure, and functional activity. (A) In vitro pSTAT3 functional activity of r‐Leptin with the human long‐form leptin receptor annotated with concentrations achieved in this study and published clinical studies ( n = 2–4 independent runs). (B) Compilation of plasma leptin levels correlated to fat mass achieved in this study with different degrees of weight loss and dietary fat levels.

Article Snippet: Mouse recombinant leptin (r‐leptin) was purchased from R & D Systems (Minneapolis, MN).

Techniques: Functional Assay, Activity Assay, In Vitro, Clinical Proteomics