Deletion of p22phox-dependent oxidative stress in the hypothalamus protects against obesity by modulating β3-adrenergic mechanisms
Heinrich E. Lob, … , Allyn L. Mark, Robin L. Davisson
Heinrich E. Lob, … , Allyn L. Mark, Robin L. Davisson
Published January 26, 2017
Citation Information: JCI Insight. 2017;2(2):e87094. https://doi.org/10.1172/jci.insight.87094.
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Research Article Metabolism Neuroscience

Deletion of p22phox-dependent oxidative stress in the hypothalamus protects against obesity by modulating β3-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 ablate p22phox, the obligatory subunit for NADPH oxidase activity, in mice harboring a conditional p22phox allele. Selective deletion of p22phox in 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

Heinrich E. Lob, Jiunn Song, Chansol Hurr, Alvin Chung, Colin N. Young, Allyn L. Mark, Robin L. Davisson

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Figure 4

Reduction in p22phox in the periventricular nucleus (PVN) arrests further weight gain in obese animals.

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Reduction in p22phox in the periventricular nucleus (PVN) arrests furthe...
(A) Effects of PVN p22phox deletion on body weight in mice fed high-fat diet for 8 weeks prior to and 10 weeks after injection of AdLacZ or AdCre in p22phox/fl mice. (B) Average food intake before and after viral transfection in these mice. (C and D) Interscapular brown adipose tissue (iBAT) and white adipose tissue (WAT) weights taken at the termination of the experiments from the above animals (sc, subcutaneous; g, gonadal; r, renal). *P < 0.05 AdCre vs. AdLacZ, n = 7–8; 2-way ANOVA followed by a Sidak multiple comparison post-hoc test (A and B), 1-way ANOVA followed by Tukey’s post-hoc test (C and D). All data are the mean ± SEM.