{
  "abstract": "GABA-neurons are essential components of hypothalamic circuits that coordinate feeding, energy expenditure, glucose metabolism, and adaptive responses to peripheral metabolic signals. The homeodomain transcription factors Dlx5 and Dlx6 are well-established regulators of GABA-neurons development, but their contribution to the organization of metabolic control circuits remains incompletely understood. Here, we investigated the metabolic consequences of conditional Dlx5-6 deletion in VGAT-expressing GABA-neurons. Mice lacking Dlx5-6 in this lineage displayed reduced body weight and lean mass, decreased locomotor activity, and lower whole-body energy expenditure, together with altered substrate utilization. Despite this reduced metabolic expenditure, mutant mice showed improved insulin sensitivity, characterized by reduced glucose-stimulated insulin secretion and enhanced glucose lowering during insulin tolerance testing. In addition, Dlx5-6 deletion impaired the behavioral response to circulating metabolic hormones: ghrelin failed to stimulate food intake, and leptin failed to suppress refeeding after fasting. These physiological alterations were associated with developmental remodeling of hypothalamic AgRP/NPY circuitry, including an increased number of AgRP-expressing neurons at P21 and increased NPY-positive projections to selected hypothalamic and thalamic targets. In adult mice, ghrelin-induced neuronal activation was redistributed toward the median eminence, suggesting altered integration of peripheral hunger signals. Together, these findings identify Dlx5-6dependent GABAergic programs as important determinants of hypothalamic circuit organization and systemic metabolic regulation. Rather than simply controlling food intake, Dlx5-6-dependent GABAergic mechanisms appear to shape the balance between energy conservation, nutrient partitioning, hormonal responsiveness, and glucose homeostasis",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Rim Hassouna"
    },
    {
      "name": "Anthony Ansoult"
    },
    {
      "name": "Julien Castel"
    },
    {
      "name": "Nour Mesto"
    },
    {
      "name": "Sonya Yung"
    },
    {
      "name": "Raphael Denis"
    },
    {
      "name": "Giuseppe Gangarossa"
    },
    {
      "name": "Giovanni Levi"
    },
    {
      "name": "Nicolas Narboux-Nême"
    },
    {
      "name": "Claire Martin"
    },
    {
      "name": "Serge Luquet"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/45zc00n7aa3yd.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-10315915/v1",
  "fulltext_url": null,
  "id": "45zc00n7aa3yd",
  "issns": [],
  "landing_url": "https://hal.science/hal-05856873v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2807|Regulation of Appetite and Obesity"
    ]
  ],
  "openalex": "W7169622124",
  "pdf_url": "https://hal.science/hal-05856873/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/45zc00n7aa3yd.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:20:54Z",
      "native_id": "hal-05856873",
      "source": "hal",
      "url": "https://hal.science/hal-05856873v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Regulation of Appetite and Obesity",
      "subfield": "physiology"
    }
  ],
  "title": "Dlx5-6-dependent GABAergic programs shape hypothalamic control of energy balance and insulin sensitivity",
  "title_text": "Dlx5-6-dependent GABAergic programs shape hypothalamic control of energy balance and insulin sensitivity",
  "type": "preprint",
  "updated_at": "2026-11-10T12:20:54Z",
  "url": "https://research.draconitic.com/paper/45zc00n7aa3yd",
  "venue": "HAL",
  "versions": []
}