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Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis
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نویسنده
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nordström v. ,willershäuser m. ,herzer s. ,rozman j. ,von bohlen und halbach o. ,meldner s. ,rothermel u. ,kaden s. ,roth f.c. ,waldeck c. ,gretz n. ,de angelis m.h. ,draguhn a. ,klingenspor m. ,gröne h.-j. ,jennemann r.
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منبع
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plos biology - 2013 - دوره : 11 - شماره : 3
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چکیده
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Hypothalamic neurons are main regulators of energy homeostasis. neuronal function essentially depends on plasma membrane-located gangliosides. the present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (gcs; udp-glucose:ceramide glucosyltransferase). as a major mechanism of central nervous system (cns) metabolic control,we demonstrate that gcs-derived gangliosides interacting with leptin receptors (obr) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. furthermore,ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-fos) in response to alterations in peripheral energy signals. consequently,mice with inducible forebrain neuron-specific deletion of the udp-glucose:ceramide glucosyltransferase gene (ugcg) display obesity,hypothermia,and lower sympathetic activity. recombinant adeno-associated virus (raav)-mediated ugcg delivery to the arcuate nucleus (arc) significantly ameliorated obesity,specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis. © 2013 nordström et al.
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آدرس
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department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,neuherberg,germany,german center for diabetes research (dzd),neuherberg, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,neuherberg,germany,molecular nutritional medicine,else-kröner fresenius center,technische universität münchen,freising-weihenstephan,germany,german center for diabetes research (dzd),neuherberg, Germany, institute for anatomy and cell biology,university of greifswald,greifswald, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, institute for physiology and pathophysiology,heidelberg university,heidelberg, Germany, institute for physiology and pathophysiology,heidelberg university,heidelberg, Germany, medical research center,heidelberg university,heidelberg, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,neuherberg,germany,german center for diabetes research (dzd),neuherberg,germany,technische universität münchen,freising-weihenstephan, Germany, institute for physiology and pathophysiology,heidelberg university,heidelberg, Germany, molecular nutritional medicine,else-kröner fresenius center,technische universität münchen,freising-weihenstephan, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany, department of cellular and molecular pathology,german cancer research center,heidelberg, Germany
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Authors
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