Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. Approach and results In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. Conclusions These findings imply that NOX4-derived ROS may play a role in the onset of insulin resista

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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