Mice Lacking NOX2 are Hyperphagic and Store Fat Preferentially in the Liver.

AJP Endocrinology and Metabolism (Impact Factor: 3.79). 04/2014; 306(12). DOI: 10.1152/ajpendo.00089.2014
Source: PubMed


Chronic low-grade inflammation is an important contributor to the development of insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Obesity and high fat feeding lead to infiltration of immune cells into metabolic tissues, promoting inflammation and insulin resistance. We hypothesized that macrophages from mice lacking NOX2 (Cybb), an essential component of the NADPH oxidase complex highly expressed in macrophages and associated with their inflammatory response, would be less inflammatory and that these mice would be protected from the development of high fat-induced insulin resistance. Bone marrow-derived macrophages from NOX2-knockout (NOX2-KO) mice expressed lower levels of inflammatory markers (Nos2, Il6); however, NOX2-KO mice were hyperphagic and gained more weight than wild-type (WT) mice when fed either a chow or a high fat (HF) diet. Surprisingly, NOX2-KO mice stored less lipid in epididymal white adipose tissue but more lipid in liver, and had higher indices of liver inflammation and macrophage infiltration compared to WT mice. Contrary to our hypothesis, HF-fed NOX2-KO mice were hyperinsulinemic and more insulin resistant compared to HF-fed WT mice, likely as a result of their higher hepatic steatosis and inflammation. In summary, NOX2 depletion promoted hyperphagia, hepatic steatosis and inflammation with either normal or high fat-feeding, exacerbating insulin resistance. We propose that NOX2 participates in food intake control and lipid distribution in mice.

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    ABSTRACT: Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals. In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response. During the last 60-100 years the life style, at least in the Western world, has changed enormously. This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer. In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues. Copyright © 2015. Published by Elsevier B.V.
    08/2015; 6. DOI:10.1016/j.redox.2015.08.016

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