Journal article
Diet-Dependent Modulation of Energy Balance by CB1 Signaling in Peripheral Sensory Neurons
iScience, Vol.28(8), 113124
08/2025
DOI: 10.1016/j.isci.2025.113124
PMCID: PMC12329259
PMID: 40777046
Abstract
Summary
The endocannabinoid system plays a pivotal role in metabolic regulation, primarily through cannabinoid receptor-1 (CB1) signaling. In this study, we show that Rimonabant (Rim), a selective non-restricted CB1 antagonist, induces substantial weight loss across multiple diet groups, although reduced food intake occurred only in the high-fat (HF) diet group. Rim enhanced brown adipose tissue (BAT) thermogenesis across all diets and visceral white adipose tissue (vWAT) thermogenesis in HF and high-carbohydrate (HC) diets. We identified CB1 expression in the gut’s splanchnic and vagal neurons and found that CB1 modulation significantly influenced afferent splanchnic but not vagal neuronal activity. Furthermore, selective splanchnic, not vagal, afferent denervation eliminated Rim’s anorectic effect. Mice lacking CB1 in sensory neurons (Nav1.8Cre/CB1flox/flox) showed reduced diet-induced weight gain and diminished metabolic response to JD5037, a peripherally restricted CB1 antagonist. These findings emphasize the importance of CB1 signaling in sensory neurons as a key mechanism regulating energy homeostasis.
Details
- Title: Subtitle
- Diet-Dependent Modulation of Energy Balance by CB1 Signaling in Peripheral Sensory Neurons
- Creators
- Benjamin Linden - University of IowaHussein Herz - University of IowaMohammad Jarrah - University of IowaDana Tasabehji - University of IowaSanaz Saleh - University of Iowa, Internal MedicineAviva Fraer - University of IowaPatrick Clark - University of Iowa, Internal MedicineYuanchao Ye - University of IowaYi Chu - University of IowaZeina Al-Khalil - American University of BeirutDonald A. Morgan - University of IowaZhiyong Zhu - University of Iowa, Internal MedicineCarlos M. Castorena - The University of Texas Southwestern Medical CenterLeonid Zingman - University of IowaKamal Rahmouni - University of IowaMohamad Mokadem - University of Iowa
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.28(8), 113124
- DOI
- 10.1016/j.isci.2025.113124
- PMID
- 40777046
- PMCID
- PMC12329259
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- CELL PRESS
- Grant note
- US Department of Veterans Affairs, VA Merit Review Program: BX004774-05 Department of Internal Medicine at the University of Iowa Carver College of MedicineUniversity of Iowa Fraternal Order of Eagles Diabetes Research CenterNIH: R01 HL162773, R01HL17294, R01 HL168752 VA: BX004249, BX006040, BX004840 University of Iowa Fraternal Order of Eagles Diabetes Research Center
We would like to thank Dr. Joel Elmquist (UT Southwestern Medical Center, Dallas, TX)for his support and for providing a key transgenic mouse model for our studies. We would also like to thank the Metabolic Phenotyping Core Facility at the University of Iowa for measurements of energy expenditure using the CLAMS and body composition assessment using Nuclear Magnetic Resonance (NMR). Finally, we would like to thank Teresa Ruggle (Senior Designer/Art Director in the internal Medicine department at the University of Iowa) for her assistance in designing schematic figures and the visual abstract.M.M. is supported by funds from the US Department of Veterans Affairs, VA Merit Review Program (BX004774-05), the Department of Internal Medicine at the University of Iowa Carver College of Medicine, and the University of Iowa Fraternal Order of Eagles Diabetes Research Center. L.Z. is supported by funds from NIH (R01 HL168752) and the VA (BX004840). K.R. is supported by funds from NIH (R01 HL162773 and R01HL17294), VA (BX004249 and BX006040), and the University of Iowa Fraternal Order of Eagles Diabetes Research Center.
- Language
- English
- Electronic publication date
- 07/2025
- Date published
- 08/2025
- Academic Unit
- Gastroenterology and Hepatology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984848017502771
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