한빛사 논문
Md Habibur Rahman1, Anup Bhusal1, Jae-Hong Kim1, Mithilesh Kumar Jha2, Gyun Jee Song3,4, Younghoon Go5, Il-Sung Jang6,7, In-Kyu Lee8,9 & Kyoungho Suk1,7,*
1BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science and Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 2Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA. 3Department of Medical Science, College of Medicine, Catholic Kwandong University, Gangneung-si, Republic of Korea. 4Translational Brain Research Center, International St. Mary’s Hospital, Catholic Kwandong University, Incheon, Republic of Korea. 5Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea. 6Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea. 7Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea. 8Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea. 9Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 700-721, Republic of Korea.
*Corresponding author
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.
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TOP52020년 후보
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