Journal: bioRxiv
Article Title: Identification of a Thermogenic Target in the Dorsal Raphe Nucleus for Weight Management
doi: 10.1101/2025.04.24.650283
Figure Lengend Snippet: (A) Schemata (created with BioRender.com ) to map activity-dependent Fos expression in mice fed a HFD for 7 days. Right panel: coronal views of the p-value of the voxel maps for Fos-positive cell densities at two different levels of DRN. White arrows indicate DRN regions significantly activated after 7 days of HFD feeding. ABA (Allen Brain Atlas) annotated image. (B) Time-course quantification of cFOS-positive neurons in the DRN of mice fed an HFD for 3 days, 2 weeks, and 16 weeks and representative immunohistochemical staining of cFOS in the DRN of mice fed an HFD for 16 weeks. (scale bar = 100um) (C) Schemata for chemogenetic inhibition of DRN VGAT neurons in vGat-IRES-Cre mice injected with CNO twice a day for 11 weeks in the preventive approach or injected daily for 17 days in DIO mice for the curative approach (right). Body weight change in mice fed a HFD for 11 weeks along with DRN VGAT neurons chemogenetic inhibition (n= 6-7 per group, P <0.0001) (middle) and body weight of DIO mice before and after chemogenetic inhibition of DRN VGAT neurons for 17 days (right) (n= 6-7 per group, P <0.0001). (D-G) (n= 6-7 per group, P < 0.05), Metabolic phenotyping of vGat-IRES-Cre after completion of the preventive approach. (D) Adiposity (% total body weight) (E) Average food intake (F) Interscapular BAT temperature (G) Whole-body median temperature (H-K) Indirect calorimetry of DIO Vgat-IRES-Cre mice injected inhibitory DREADDs and placed in metabolic cages for measurement of (H) oxygen consumption (VO 2 ), oxygen dioxide production (VCO 2 ), (J) locomotion activity and (K) energy expenditure. Data are represented as mean ± s.e.m. P values were calculated using a or an unpaired two-tailed Student’s t -test ( A, D-G ), two-way ANOVA with a multiple-comparisons test using a Tukey post-hoc approach ( C ) or using CalR software and a two-sided ANCOVA regression analysis taking body weight into account ( H-K ). P < 0.05 is considered significant. The CNO dose used was 1 mg/kg.
Article Snippet: Energy expenditure was assessed through measurement by indirect calorimetry of oxygen consumption (VO2), carbon dioxide production (VCO2), heat production, and locomotor activity using an automated home cage phenotyping system (TSE Systems).
Techniques: Activity Assay, Expressing, Immunohistochemical staining, Staining, Inhibition, Injection, Two Tailed Test, Software