---
title: "Triglyceride signaling modulates nucleus accumbens D2R neuron responses during appetitive behaviors"
id: "biorxiv-12-central-lipid-sensing-tunes-accumbal-d2r-neuron-activity-in-appetitive"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-12-central-lipid-sensing-tunes-accumbal-d2r-neuron-activity-in-appetitive"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1?rss=1"
published_at: "2026-09-23T09:50:14.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Triglyceride signaling modulates nucleus accumbens D2R neuron responses during appetitive behaviors
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-12-central-lipid-sensing-tunes-accumbal-d2r-neuron-activity-in-appetitive
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1?rss=1)
- **Published At:** 2026-09-23T09:50:14.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Peripheral metabolic signals and central reward circuits are connected; circulating **triglycerides (TG)** act as neuromodulators of mesolimbic dopamine and reward processing. - The study assessed whether central TG availability directly alters activity of nucleus accumbens (**NAc**) dopamine D2 receptor-expressing spiny projection neurons (**D2R-SPNs**) during appetitive behaviors. - Using in vivo **fiber photometry** in Drd2-Cre mice, the authors recorded D2R-SPN calcium dynamics across Pavlovian conditioning and refeeding paradigms. - During learning, D2R-SPNs developed robust responses to a reward-predictive conditioned stimulus (CS+); activity during reward consumption remained stable across sessions. - Acute elevation of central TG via **carotid infusion** in lean chow-fed mice did not change D2R-SPN activity or behavioral performance, whether mice were fed or food-restricted. - In contrast, mice with prior exposure to a **high-fat diet (HFD)** showed metabolic state–dependent sensitivity: central TG delivery suppressed cue-evoked D2R-SPN activity in food-restricted HFD mice without altering reward consumption or measured behavioral outputs. - Similarly, TG reduced refeeding-evoked D2R-SPN activation in fasted HFD-exposed mice, while responses to novelty were unaffected. - Overall, obesogenic dietary history reveals a context-dependent modulation of accumbal D2R-SPNs by circulating lipids, indicating an interaction between past diet, current metabolic state, and neural encoding of reward cues and food-directed behaviors.
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Guangping Li Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Guangping%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20G&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AGuangping%2BLi%2B) * [ORCID record for Guangping Li](http://orcid.org/0009-0004-4717-6211 "Open in new tab") Julien Castel Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Julien%2BCastel%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Castel%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJulien%2BCastel%2B) * [ORCID record for Julien Castel](http://orcid.org/0000-0003-4309-701X "Open in new tab") Anthony Ansoult Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anthony%2BAnsoult%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ansoult%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnthony%2BAnsoult%2B) * [ORCID record for Anthony Ansoult](http://orcid.org/0009-0008-2386-4908 "Open in new tab") Benoit Bertrand Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Benoit%2BBertrand%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bertrand%20B&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ABenoit%2BBertrand%2B) * [ORCID record for Benoit Bertrand](http://orcid.org/0009-0005-9833-5945 "Open in new tab") Giuseppe Gangarossa Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Giuseppe%2BGangarossa%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gangarossa%20G&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AGiuseppe%2BGangarossa%2B) * [ORCID record for Giuseppe Gangarossa](http://orcid.org/0000-0001-9045-2139 "Open in new tab") * For correspondence: giuseppe.gangarossa@u-paris.fr Serge Luquet Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Serge%2BLuquet%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Luquet%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASerge%2BLuquet%2B) * [ORCID record for Serge Luquet](http://orcid.org/0000-0001-8668-6645 "Open in new tab") * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5802674/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5802674/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5802674/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5802674/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5802674/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Energy homeostasis and motivated behaviours are tightly interconnected processes coordinated by peripheral metabolic signals and central reward circuits. Among these signals, circulating triglycerides (TG) have emerged as neuromodulators of mesolimbic dopamine functions and reward processing. However, whether TG directly regulate the activity of defined neuronal populations within the nucleus accumbens (NAc) during appetitive behaviours remains unknown. Here, we investigated how central TG availability shapes the in vivo activity of NAc dopamine D2 receptor-expressing spiny projection neurons (D2R-SPNs) across distinct nutritional and metabolic states. Using in vivo fiber photometry in Drd2-Cre mice, we monitored D2R-SPN Ca2+ dynamics during appetitive Pavlovian conditioning and refeeding. D2R-SPNs progressively developed robust responses to a reward-predictive conditioned stimulus (CS+) over the course of learning, while their activity during reward consumption remained stable. Acute elevation of central TG levels through carotid infusion did not alter D2R-SPN activity or behavioural performance in lean chow-fed mice, irrespective of whether they were fed or food-restricted. In contrast, in mice exposed to a high-fat diet (HFD), central TG delivery suppressed cue-evoked D2R-SPN activity in food-restricted animals without affecting reward consumption or behavioural outputs. Likewise, TG significantly reduced refeeding-evoked D2R-SPN activation in fasted HFD-mice, while leaving novelty-induced neuronal responses unchanged. Together, these findings demonstrate that obesogenic conditions reveal a metabolic state-dependent sensitivity of accumbal D2R-SPNs to circulating lipids. This work identifies TG as context-dependent modulators of D2R-SPN function and uncovers a mechanism through which dietary history interacts with current metabolic state to reshape the neural encoding of reward-predictive cues and food-directed behaviours. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Agence Nationale de la Recherche, https://ror.org/00rbzpz17 Fondation pour la Recherche Médicale, https://ror.org/04w6kn183 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/09/23/2026.09.21.753293.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.09.21.753293v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Central lipid sensing tunes accumbal D2R-neuron activity in appetitive behaviours Guangping Li, Julien Castel, Anthony Ansoult, Benoit Bertrand, Giuseppe Gangarossa, Serge Luquet bioRxiv 2026.09.21.753293; doi: https://doi.org/10.64898/2026.09.21.753293 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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