title: Deletion of p22phox-dependent oxidative stress in the hypothalamus protects against obesity by modulatingβ3-adrenergic mechanisms.
abstract: A role for oxidative stress in the brain has been suggested in the pathogenesis of diet-induced obesity (DIO), although the underlying neural regions and mechanisms remain incompletely defined. We tested the hypothesis that NADPH oxidase-dependent oxidative stress in the paraventricular nucleus (PVN), a hypothalamic energy homeostasis center, contributes to the development of DIO. Cre/LoxP technology was coupled with selective PVN adenoviral microinjection to ablatep22phox, the obligatory subunit for NADPH oxidase activity, in mice harboring a conditionalp22phoxallele. Selective deletion ofp22phoxin the PVN protected mice from high-fat DIO independent of changes in food intake or locomotor activity. This was accompanied by β3-adrenoceptor-dependent increases in energy expenditure, elevations in brown adipose tissue thermogenesis, and browning of white adipose tissue. These data reveal a potentially novel role for brain oxidative stress in the development of DIO by modulating β3-adrenoceptor mechanisms and point to the PVN as an underlying neural site.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Heinrich E
authors.initials: HE
authors.lastname: Lob
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Jiunn
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Chansol
authors.initials: C
authors.lastname: Hurr
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Chung
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.|Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Colin N
authors.initials: CN
authors.lastname: Young
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.|Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Allyn L
authors.initials: AL
authors.lastname: Mark
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.|Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Davisson
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003573:Cytochrome b Group / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism; D008124:Locomotion; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D022722:Thermogenesis / Q000235:genetics*
chemical_list: D003573:Cytochrome b Group; D022702:Receptors, Adrenergic, beta-3; D019255:NADPH Oxidases; C515614:Cyba protein, mouse