Journal: bioRxiv

Article Title: Hippocampal CA3 Nex/Neurod6 + neuron-specific TNFR2 alleviates chronic neuropathic pain by sex-dependently engaging opioid and endocannabinoid pathways

doi: 10.1101/2025.11.24.690195

Figure Lengend Snippet: CB1 receptor blockade using AM251 prevents TNFR2 Agonist-driven recovery after CCI in both sexes and reveals sex-divergent hippocampal NF-κB/CREB signaling. (A) Timeline of the experiment (created in Biorender). After CCI, at dpi 7, 10, and 13, mice were administered (i.p.) either with TNFR2 Agonist (10mg/kg) or PBS, and the CB1 receptor antagonist AM251 (i.p.) was given at dpi 7, 14, and 21. Longitudinal von Frey withdrawal thresholds after CCI in males (B) and females (C) (n=10 each group/sex). (D-E) Hippocampal western blots and quantification for males: phospho-NF-κB (D) and phospho-CREB (E) . In males, TNFR2 agonism elevated p-p65 and p-CREB relative to Naïve and CCI+PBS; AM251 reduced both toward or below baseline (n=4-5 each group). (F-G) Hippocampal western blots and quantification for females phospho-NF-κB (F) and p-CREB (G) . In females, TNFR2 agonism and AM251 co-treatment reduced p-p65 relative to Naïve and CCI+PBS,; p-CREB levels were elevated after CCI and reduced by TNFR2 agonism and AM251 co-treatment (n=4-5 each group). Data are represented as mean ± SEM; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Article Snippet: The CB1 receptor antagonist AM251 (MedChemExpress HY-15443; 10 mg/kg, i.p.) was prepared in DMSO (Sigma-Aldrich 34869) and corn oil (Thermo Fisher 8001-30-7) and given on dpi 14, 21, and 28.

Techniques: Western Blot

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Localization of CB1 receptor within afferent/sensory neurons CB1 immunostaining of cross-sections of the celiac ganglion, nodose ganglion, and thoracic (T10) dorsal root ganglion of Nav.1.8-tdTomato mice (CB1 = green, Nav1.8-tdTomato = red, DAPI = blue. (A) 20×; scale bars, 50 μm and (B) 100×; scale bars, 10 μm. n = 4–5 mice.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of CB1 agonist/antagonist on direct neuronal activity of splanchnic vs. vagal afferent fibers (A and B) Direct multi-fiber recording of afferent splanchnic nerve activity following administration of (A) rimonabant (Rim) vs. vehicle (Veh) or (B) anandamide (AEA) vs. Veh. (C and D) Direct multi-fiber recording of afferent vagal nerve activity following administration of (C) Rim vs. Veh or (D) AEA vs. Veh. A representative neurogram on the left side corresponds to each intervention at times 30 and 60 min. n = 7–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare the means of each diet. Statistical significances are denoted with asterisks: ∗p ≤ 0.05.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Activity Assay

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of splanchnic versus vagal sensory denervation on energy balance in response to cb1 antagonism (A) Schematic display of experiments examining the effects of CB1 antagonist (rimonabant) in mice with selective splanchnic vs. vagal afferent denervation. (B) Absolute body weights expressed in grams (g) (left) and percent (%) weight changes from baseline (right) after 20 days of rimonabant vs. vehicle administration in sham denervated, afferent splanchnic denervated, and afferent vagal denervated high-fat diet-induced obese C57BL/6J mice. (C) Average daily food intake expressed in (Kcal/day) during week 1 (left) and week 3 (right) of rimonabant vs. vehicle administration in sham-denervated, afferent splanchnic denervated, and afferent vagal denervated C57BL/6J mice. All results are presented as mean ± SEM (error bars). n = 6–8. One-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques:

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the anorectic effect of cb1 antagonism (A) CB1 immunostaining (red) in thoracic-T10 dorsal root ganglion (DRG), nodose ganglion, and hippocampus of 12-week-old male Nav1.8-Cre + /CB1 flox/flox (Nav1.8-CB1 +/+ ) and Nav1.8-Cre − /CB1f lox/flox (Nav1.8-CB1 −/− ) mice. Scale bars, 20 μm. (B) Body weight in (g) over time, average daily food intake in (Kcal/day), % weight change from baseline over time, and % weight gain after 3 weeks (21 days) of HF diet feeding in Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice. (C and D) Body weight changes (expressed in grams [g] and percent [%]) and average daily food intake (measured over 3 days during week 1) in HF diet-fed (C) Nav1.8-CB1 +/+ and (D) Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD5037) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 6–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare means between two groups, and one-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the thermogenic effect of CB1 antagonism in visceral WAT TH and UCP1 co-expression—assessed by immunofluorescence (IF) in HF diet-fed Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 3–4. DAPI = blue, TH = green, UCP1 = red. Scale bars, 20 μm.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Expressing, Immunofluorescence

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: The effect of rimonabant on measurements of energy balance across different diet groups (A) Weight change in (g) over time in (days). (B) Percent (%) change from baseline in total body weight at day 15. (C) Average daily food intake in (Kcal/day) measured during week 1 (over 3 days period). (D) Feeding efficiency displayed in (mg of weight change/Kcal consumed) over 15 days. (E) UCP1 mRNA expression in visceral white adipose tissue (vWAT) and brown adipose tissue (BAT) of C57BL/6J male mice placed on regular chow (RC), high-carbohydrate (HC), and high-fat (HF) diets and given vehicle vs. rimonabant for 15 days. All results are presented as mean ± SEM (error bars). n = 5–7. Student’s t test was used to compare means of each diet intervention. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.001; and ∗∗∗∗p ≤ 0.0001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Expressing

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Thermogenic effect of rimonabant on brown and white adipose tissue across different diets (A and B) Immunohistochemical staining of UPC1 (reddish-brown) in (A) brown adipose tissue (BAT) and (B) visceral white adipose tissue (vWAT) of rimonabant vs. vehicle-treated C57BL/6J mice across several diet groups. RC, regular chow HC, high carbohydrates; HF, high fat. Scale bars, 100 μm. (C) In vivo recording of body heat temperature—measured by infrared (IR) camera—from the backside (BAT localized region [left]) and the frontside (vWAT localized region [right]) of C57BL/6J mice, 60 min after administration of rimonabant vs. vehicle across several diet groups. The colored heat grade legend is displayed below IR images. n = 3–4.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunohistochemical staining, Staining, In Vivo

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Localization of CB1 receptor within afferent/sensory neurons CB1 immunostaining of cross-sections of the celiac ganglion, nodose ganglion, and thoracic (T10) dorsal root ganglion of Nav.1.8-tdTomato mice (CB1 = green, Nav1.8-tdTomato = red, DAPI = blue. (A) 20×; scale bars, 50 μm and (B) 100×; scale bars, 10 μm. n = 4–5 mice.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of CB1 agonist/antagonist on direct neuronal activity of splanchnic vs. vagal afferent fibers (A and B) Direct multi-fiber recording of afferent splanchnic nerve activity following administration of (A) rimonabant (Rim) vs. vehicle (Veh) or (B) anandamide (AEA) vs. Veh. (C and D) Direct multi-fiber recording of afferent vagal nerve activity following administration of (C) Rim vs. Veh or (D) AEA vs. Veh. A representative neurogram on the left side corresponds to each intervention at times 30 and 60 min. n = 7–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare the means of each diet. Statistical significances are denoted with asterisks: ∗p ≤ 0.05.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Activity Assay

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of splanchnic versus vagal sensory denervation on energy balance in response to cb1 antagonism (A) Schematic display of experiments examining the effects of CB1 antagonist (rimonabant) in mice with selective splanchnic vs. vagal afferent denervation. (B) Absolute body weights expressed in grams (g) (left) and percent (%) weight changes from baseline (right) after 20 days of rimonabant vs. vehicle administration in sham denervated, afferent splanchnic denervated, and afferent vagal denervated high-fat diet-induced obese C57BL/6J mice. (C) Average daily food intake expressed in (Kcal/day) during week 1 (left) and week 3 (right) of rimonabant vs. vehicle administration in sham-denervated, afferent splanchnic denervated, and afferent vagal denervated C57BL/6J mice. All results are presented as mean ± SEM (error bars). n = 6–8. One-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques:

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the anorectic effect of cb1 antagonism (A) CB1 immunostaining (red) in thoracic-T10 dorsal root ganglion (DRG), nodose ganglion, and hippocampus of 12-week-old male Nav1.8-Cre + /CB1 flox/flox (Nav1.8-CB1 +/+ ) and Nav1.8-Cre − /CB1f lox/flox (Nav1.8-CB1 −/− ) mice. Scale bars, 20 μm. (B) Body weight in (g) over time, average daily food intake in (Kcal/day), % weight change from baseline over time, and % weight gain after 3 weeks (21 days) of HF diet feeding in Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice. (C and D) Body weight changes (expressed in grams [g] and percent [%]) and average daily food intake (measured over 3 days during week 1) in HF diet-fed (C) Nav1.8-CB1 +/+ and (D) Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD5037) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 6–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare means between two groups, and one-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the thermogenic effect of CB1 antagonism in visceral WAT TH and UCP1 co-expression—assessed by immunofluorescence (IF) in HF diet-fed Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 3–4. DAPI = blue, TH = green, UCP1 = red. Scale bars, 20 μm.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Expressing, Immunofluorescence

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Localization of CB1 receptor within afferent/sensory neurons CB1 immunostaining of cross-sections of the celiac ganglion, nodose ganglion, and thoracic (T10) dorsal root ganglion of Nav.1.8-tdTomato mice (CB1 = green, Nav1.8-tdTomato = red, DAPI = blue. (A) 20×; scale bars, 50 μm and (B) 100×; scale bars, 10 μm. n = 4–5 mice.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of CB1 agonist/antagonist on direct neuronal activity of splanchnic vs. vagal afferent fibers (A and B) Direct multi-fiber recording of afferent splanchnic nerve activity following administration of (A) rimonabant (Rim) vs. vehicle (Veh) or (B) anandamide (AEA) vs. Veh. (C and D) Direct multi-fiber recording of afferent vagal nerve activity following administration of (C) Rim vs. Veh or (D) AEA vs. Veh. A representative neurogram on the left side corresponds to each intervention at times 30 and 60 min. n = 7–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare the means of each diet. Statistical significances are denoted with asterisks: ∗p ≤ 0.05.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Activity Assay

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: Effects of splanchnic versus vagal sensory denervation on energy balance in response to cb1 antagonism (A) Schematic display of experiments examining the effects of CB1 antagonist (rimonabant) in mice with selective splanchnic vs. vagal afferent denervation. (B) Absolute body weights expressed in grams (g) (left) and percent (%) weight changes from baseline (right) after 20 days of rimonabant vs. vehicle administration in sham denervated, afferent splanchnic denervated, and afferent vagal denervated high-fat diet-induced obese C57BL/6J mice. (C) Average daily food intake expressed in (Kcal/day) during week 1 (left) and week 3 (right) of rimonabant vs. vehicle administration in sham-denervated, afferent splanchnic denervated, and afferent vagal denervated C57BL/6J mice. All results are presented as mean ± SEM (error bars). n = 6–8. One-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques:

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the anorectic effect of cb1 antagonism (A) CB1 immunostaining (red) in thoracic-T10 dorsal root ganglion (DRG), nodose ganglion, and hippocampus of 12-week-old male Nav1.8-Cre + /CB1 flox/flox (Nav1.8-CB1 +/+ ) and Nav1.8-Cre − /CB1f lox/flox (Nav1.8-CB1 −/− ) mice. Scale bars, 20 μm. (B) Body weight in (g) over time, average daily food intake in (Kcal/day), % weight change from baseline over time, and % weight gain after 3 weeks (21 days) of HF diet feeding in Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice. (C and D) Body weight changes (expressed in grams [g] and percent [%]) and average daily food intake (measured over 3 days during week 1) in HF diet-fed (C) Nav1.8-CB1 +/+ and (D) Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD5037) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 6–8. All results are presented as mean ± SEM (error bars). Student’s t test was used to compare means between two groups, and one-way ANOVA was used to compare means between interventions. Statistical significances are denoted with asterisks as follows: ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.0001, and ∗∗∗∗p ≤ 0.00001.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Immunostaining

Journal: iScience

Article Title: Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons

doi: 10.1016/j.isci.2025.113124

Figure Lengend Snippet: CB1 deletion in sensory neurons eliminates the thermogenic effect of CB1 antagonism in visceral WAT TH and UCP1 co-expression—assessed by immunofluorescence (IF) in HF diet-fed Nav1.8-CB1 +/+ and Nav1.8-CB1 −/− male mice after 15 days of administration of peripherally restricted CB1 antagonist (JD) vs. non-restricted CB1 antagonist (Rim) vs. vehicle (Veh). n = 3–4. DAPI = blue, TH = green, UCP1 = red. Scale bars, 20 μm.

Article Snippet: Nav1.8 Cre+ /CB1 flox/flox and Nav1.8 Cre− /CB1 flox/flox were started on HF diet starting at 6 weeks of age for 6 weeks before dividing each group into three subgroups, receiving the non-selective CB1 inverse agonist Rimonabant (SR 141716A) at a dose of 10 mg/Kg/day, or the peripheral-restricted CB1 inverse agonist JD5037 (MedChem Express) at a dose of 3 mg/Kg/day, , or vehicle of equivalent volume by oral gavage for 15 days.

Techniques: Expressing, Immunofluorescence