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

Md Habibur Rahman, Anup Bhusal, Jae-Hong Kim, Mithilesh Kumar Jha, Gyun Jee Song, Younghoon Go, Il-Sung Jang, In-Kyu Lee and Kyoungho Suk ()
Additional contact information
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
Younghoon Go: Korea Institute of Oriental Medicine
Il-Sung Jang: Kyungpook National University
In-Kyu Lee: Kyungpook National University Hospital
Kyoungho Suk: Kyungpook National University

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19576-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19576-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19576-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().