{
  "abstract": "Metabolites are increasingly recognized as circulating molecules that regulate physiology, yet the mechanisms that couple intracellular production to organism-wide action remain poorly defined. Using the anorexigenic metabolite Lac-Phe as a tractable system, we identify the orphan transporter MCT6 (SLC16A5) as a physiologic intestinal Lac-Phe exporter. This mechanism controls the extent to which intracellularly synthesized Lac-Phe acquires systemic activity. MCT6 transports Lac-Phe, mediates its cellular efflux, and is required for maintaining its blood levels in mice following strong glycolytic stimuli. Both global and intestinal epithelial-specific deletion of MCT6 confers resistance to metformin-associated weight loss on a high-fat diet. Bypassing the transport defect with exogenous Lac-Phe normalizes the body weight phenotype of MCT6-KO mice. Together, these data connect MCT6 to metformin pharmacology and intestinal lactate metabolism, and more generally underscore the importance of transporter-mediated release in the conversion of an intracellular metabolic state into a circulating metabolite effector.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Wu Tsai Human Perfor"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "S. Xiao"
    },
    {
      "name": "A. S.-H. Tung"
    },
    {
      "name": "J. Spaas"
    },
    {
      "name": "S. Fu"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "T. K. Trinh"
    },
    {
      "name": "M. D. Moya-Garzon"
    },
    {
      "name": "V. L. Li"
    },
    {
      "name": "H. T. Cessna"
    },
    {
      "name": "K. Ito"
    },
    {
      "name": "S. C. Reghupathy"
    },
    {
      "name": "C. Lin"
    },
    {
      "name": "X. Lyu"
    },
    {
      "name": "S. H. Raun"
    },
    {
      "name": "M. D. W. Tyner"
    },
    {
      "name": "A. Germakovski"
    },
    {
      "name": "J. Tondreau"
    },
    {
      "name": "M. Yeckley"
    },
    {
      "name": "W. Wei"
    },
    {
      "name": "M. R. Howitt"
    },
    {
      "name": "M. D. Parker"
    },
    {
      "name": "J. A. Sprowl"
    },
    {
      "name": "S. M. Hinshaw"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Z. Long"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3ae65ht91r5vb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753556",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753556v1.full",
  "id": "3ae65ht91r5vb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753556v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "physiology"
    ],
    [
      "openalex",
      "1312|Metabolism, Diabetes, and Cancer"
    ]
  ],
  "openalex": "W7214579046",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753556v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3ae65ht91r5vb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:53Z",
      "native_id": "10.64898/2026.09.22.753556",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753556v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss",
  "title_text": "MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:53Z",
  "url": "https://research.draconitic.com/paper/3ae65ht91r5vb",
  "venue": "bioRxiv",
  "versions": []
}