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Gao, Y. ; Layritz, C. ; Legutko, B. ; Eichmann, T.O.* ; Laperrousaz, E.* ; Moullé, V.S.* ; Cruciani-Guglielmacci, C.* ; Magnan, C.* ; Luquet, S.* ; Woods, S.C.* ; Eckel, R.H.* ; Yi, C.-X. ; Garcia-Caceres, C. ; Tschöp, M.H.

Disruption of lipid uptake in astroglia exacerbates diet induced obesity.

Diabetes 66, 2555-2563 (2017)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
Neuronal circuits in the brain help to control feeding behavior and systemic metabolism in response to afferent nutrient and hormonal signals. Although astrocytes have historically been assumed to be less relevant for such neuroendocrine control, we asked whether lipid uptake via lipoprotein lipase (LPL) in astrocytes is required for the central regulation of energy homeostasis. Ex vivo studies with hypothalamic-derived astrocytes showed that LPL expression is up-regulated by oleic acid; whereas it is decreased in response to palmitic acid or triglyceride. Likewise, astrocytic LPL deletion reduced the accumulation of lipid drops in those glial cells. Consecutive in vivo studies showed that the postnatal ablation of LPL in glial fibrillary acidic protein (GFAP)-expressing astrocytes induced exaggerated body weight gain and glucose intolerance in mice exposed to a high-fat diet (HFD). Intriguingly, astrocytic LPL deficiency also triggered increased ceramide content in the hypothalamus, which may contribute to hypothalamic insulin resistance. We conclude that hypothalamic LPL functions in astrocytes to ensure appropriately balanced nutrient sensing, ceramide distribution, body weight regulation and glucose metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Neural Stem-cells; Lipoprotein-lipase; Fatty-acids; Food-intake; Hypothalamic Neurons; Insulin-resistance; Glucose-production; Developing Brain; Energy-balance; In-vivo
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 66, Heft: 10, Seiten: 2555-2563 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)