Mice lacking NOX2 are hyperphagic and store fat preferentially in the liver.

Abstract

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 immune cells 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 indexes of liver inflammation and macrophage infiltration than WT mice. Contrary to our hypothesis, HF-fed NOX2-KO mice were hyperinsulinemic and more insulin resistant than 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.

• Authors: Sheila R Costford, Jason Castro-Alves, Kenny L Chan, Liane J Bailey, Minna Woo, Denise D Belsham, John H Brumell, Amira Klip
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 306 Issue 12 Pg. E1341-53 (Jun 15 2014) ISSN: 1522-1555 [Electronic] United States
• PMID: 24760992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Membrane Glycoproteins
• Cybb protein, mouse
• NADPH Oxidase 2
• NADPH Oxidases

Topics

• Adipose Tissue, White (immunology, metabolism, pathology)
• Animals
• Appetite Regulation
• Appetitive Behavior
• Behavior, Animal
• Cells, Cultured
• Diabetes Mellitus, Type 2 (complications, etiology)
• Diet, High-Fat (adverse effects)
• Fatty Liver (complications, etiology)
• Hyperphagia (immunology, metabolism, pathology, physiopathology)
• Insulin Resistance
• Lipid Metabolism
• Liver (immunology, metabolism, pathology)
• Macrophages (immunology, metabolism, pathology)
• Male
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• NADPH Oxidase 2
• NADPH Oxidases (genetics, metabolism)
• Non-alcoholic Fatty Liver Disease
• Obesity (complications, etiology)