Endothelial Nox5 Expression Modulates Glucose Uptake and Lipid Accumulation in Mice Fed a High-Fat Diet and 3T3-L1 Adipocytes Treated with Glucose and Palmitic Acid.

Jorge G García,Fermín I Milagro,Guillermo Zalba,Carlos De Miguel,Eduardo Ansorena

doi:10.3390/ijms22052729

Abstract

Obesity is a global health issue associated with insulin resistance and altered lipid homeostasis. It has been described that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity are involved in the development of these pathologies. The present study describes the role of endothelial NOX5 expression over adipose tissue by using two experimental systems: NOX5 conditional knock-in mice fed with a high-fat diet and 3T3-L1 adipocytes cultured with conditioned media of NOX5-expressing endothelial cells previously treated with glucose and palmitic acid. Animals expressing NOX5 presented lower body weight gain and less mesenteric and epididymal adipose mass compared to control mice fed with the same diet. NOX5-expressing mice also showed significantly lower glycaemia and improved insulin-induced glucose uptake. In addition, Glut4 and Caveolin 1 (Cav1) expression were significantly increased in the adipose tissue of these animals. Likewise, 3T3-L1 adipocytes treated with conditioned media from NOX5-expressing endothelial cells, incubated with high glucose and palmitic acid, presented a reduction in lipid accumulation and an increase in glucose uptake. Moreover, a significant increase in the expression of Glut4 and Cav1 was also detected in these cells. Taken together, all these data support that, in response to a highly caloric diet, NOX5 endothelial activity may regulate glucose sensitivity and lipid homeostasis in the adipose tissue.

Highlights

Obesity is considered a global health issue characterised by an increase in body weight that results in an excessive fat accumulation, disrupting adipose tissue homeostasis [1].Obesity could lead to metabolic syndrome development, insulin resistance, and type2 diabetes, which in turn might develop into liver and cardiovascular disorders. [2]
Endothelial NOX5-expressing mice fed with the high-fat diet (HFD) presented lower body weight gain than their control CRE counterparts
One of the circumstances generally associated with obesity is oxidative stress, which is the result of an imbalance between reactive oxygen species (ROS) production and degradation [27]

Summary

Introduction

Obesity is considered a global health issue characterised by an increase in body weight that results in an excessive fat accumulation, disrupting adipose tissue homeostasis [1].Obesity could lead to metabolic syndrome development, insulin resistance, and type2 diabetes, which in turn might develop into liver and cardiovascular disorders. [2]. Obesity could lead to metabolic syndrome development, insulin resistance, and type. Insulin resistance is defined as a condition produced by the low or inexistent response to high levels of insulin in the organism. Insulin binds to insulin receptors (IR), promoting its activation and its auto-phosphorylation, triggering the translocation of glucose transporter protein (GLUT4) to the cell membrane [3]. Effective insulin signalling in adipocytes may be primarily dependent on the localization of insulin responsive elements (IR and GLUT4) to caveolae, small invaginations of the plasma membrane that are especially abundant in this type of cell. Caveolae, considered signalling platforms, facilitate a rapid activation of IR improving signal transduction [4]. The main structural and functional components of caveolae are caveolins, cholesterol-dependent integral membrane proteins [5]

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