Adipocyte DIO2 Expression Increases in Human Obesity but Is Not Related to Systemic Insulin Sensitivity.

David Bradley,Valerie Wright,Sabrena Noria,Anahita Jalilvand,Joey Liu,Alecia Blaszczak,Willa Hsueh,David Renton,Bradley Needleman

doi:10.1155/2018/2464652

David Bradley, Valerie Wright + Show 7 more

Open Access

https://doi.org/10.1155/2018/2464652

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Abstract

Deiodinase type II (D2), encoded by DIO2, catalyzes the conversion of T4 to bioactive T3. T3 not only stimulates adaptive thermogenesis but also affects adipose tissue (AT) lipid accumulation, mitochondrial function, inflammation, and potentially systemic metabolism. Although better defined in brown AT, the precise role of DIO2 expression in white AT remains largely unknown, with data derived only from whole fat. Therefore, the purpose of this study was to determine whether subcutaneous (SAT) and visceral (VAT) adipocyte-specific gene expression of DIO2 differs between obese and lean patients and whether these differences relate to alterations in mitochondrial function, fatty acid flux, inflammatory cytokines/adipokines, and ultimately insulin sensitivity. Accordingly, adipocytes of 73 obese and 21 lean subjects were isolated and subjected to gene expression analyses. Our results demonstrate that obese compared to lean human individuals have increased adipocyte-specific DIO2 expression in both SAT and VAT. Although higher DIO2 was strongly related to reduced fatty acid synthesis/oxidation and mitochondrial function, we found no relationship to proinflammatory cytokines or insulin resistance and no difference based on diabetic status. Our results suggest that adipocyte-derived DIO2 may play a role in weight maintenance but is likely not a major contributor to obesity-related insulin resistance.

Highlights

In spite of growing recognition, the obesity epidemic continues unabated in the United States (US)
The main purpose of this study was to test the hypothesis that SAT and VAT adipocyte gene expression of DIO2 differs between obese and lean human adipose tissue (AT) and that these differences will relate to (1) insulin resistance and (2) expression of genes involved in mitochondrial function, fatty acid flux, and inflammation
There was no difference in age between the lean and obese patient groups

Summary

Introduction

In spite of growing recognition, the obesity epidemic continues unabated in the United States (US). Over 2/3 of the US adult population is considered overweight or obese [1, 2]. Obesity contributes to excess morbidity and mortality and adversely affects nearly every organ in the body [3]. With a growing appreciation for the negative health consequences, current treatment options for obesity and its complications remain insufficient and the underlying mechanisms behind obesity-induced complications have yet to be elucidated. Obesity fundamentally results when caloric intake exceeds total energy expenditure [4]. The role of nonshivering or adaptive thermogenesis (the generation of heat through uncoupling of mitochondrial respiration) in total energy expenditure is being appreciated [5], with obese individuals demonstrating a reduced adaptive thermogenic capacity [6]

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