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Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes

Author

Listed:
  • Md Habibur Rahman

    (Kyungpook National University)

  • Anup Bhusal

    (Kyungpook National University)

  • Jae-Hong Kim

    (Kyungpook National University)

  • Mithilesh Kumar Jha

    (Johns Hopkins University)

  • Gyun Jee Song

    (Catholic Kwandong University
    Catholic Kwandong University)

  • Younghoon Go

    (Korea Institute of Oriental Medicine)

  • Il-Sung Jang

    (Kyungpook National University
    Kyungpook National University)

  • In-Kyu Lee

    (Kyungpook National University Hospital
    Kyungpook National University)

  • Kyoungho Suk

    (Kyungpook National University
    Kyungpook National University)

Abstract

Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior.

Suggested Citation

  • Md Habibur Rahman & Anup Bhusal & Jae-Hong Kim & Mithilesh Kumar Jha & Gyun Jee Song & Younghoon Go & Il-Sung Jang & In-Kyu Lee & Kyoungho Suk, 2020. "Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19576-1
    DOI: 10.1038/s41467-020-19576-1
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