Abstract

The hyperproduction of oxidative stress and inflammatory biomarkers, which is paralleled by decreased levels of antioxidant and anti-inflammatory mediators, is part of cellular mechanisms that contribute to the disruption of metabolic homeostasis in obesity. Whether gender-specific alterations and gender-restricted associations in these biomarkers underlie the increased cardiometabolic risk in men compared to women is unclear. We enrolled 31 women and 29 men, aged ≥50 and ≤70 years and with body mass index ≥ 30 and <40 kg/m2. We assessed the concentrations of aminothiols (cysteine, homocysteine, and glutathione), expression of oxidant/antioxidant balance, adipomyokines (leptin, adiponectin, myostatin, and interleukin-6), markers of chronic inflammation, and vitamin D, an index of nutritional state, in plasma and serum samples by using HPLC, ELISA, and chemiluminescent immunoassay methods. We measured insulin resistance (IR) by the homeostasis model assessment (HOMA) index. Despite comparable levels of visceral adiposity, IR, and a similar dietary regimen, men showed, with respect to women, higher oxidant concentrations and lower antioxidant levels, which paralleled IR severity. Myostatin levels correlated with prooxidant aminothiols among men only. Gender-specific alterations in aminothiol status and adipomyokine profile and the gender-restricted association between these biomarkers and metabolic derangement are consistent with an increased cardiometabolic risk in men compared to age-matched women with stage I-II obesity. Strict control of redox and inflammatory status, even addressing gender-specific nutritional targets, may be useful to prevent obesity-related metabolic alterations and comorbidities.

Highlights

  • Obesity is a serious health problem with a worldwide impact on the risk and prognosis of several chronic diseases, such as type 2 diabetes, coronary heart disease, nonalcoholic fatty liver disease, and cancer [1]

  • Female and male groups were comparable in age, Body mass index (BMI), visceral adiposity index (VAI), homeostasis model assessment (HOMA) index, glucose, glycated haemoglobin, insulin, AST, ALT, LDL cholesterol, and triglycerides but not in HDL cholesterol concentrations that, as expected, were increased in women compared to men

  • The total forms of Hcy and Cys and ox-Hcy, ox-Cys, and ox-GSH were significantly higher in males than in females; r-GSH and vitamin D concentrations were lower in men with respect to women (Figure 1), even after exclusion of the 5 females supplemented with vitamin D

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Summary

Introduction

Obesity is a serious health problem with a worldwide impact on the risk and prognosis of several chronic diseases, such as type 2 diabetes, coronary heart disease, nonalcoholic fatty liver disease, and cancer [1]. Adverse changes associated with weight gain such as visceral obesity and physical inactivity may affect adipose and muscle tissues causing low-grade chronic inflammation and insulin resistance [2]. The mechanisms by which adipose depots expand in response to an excessive caloric intake represent a crucial determinant of the risk of metabolic dysfunction. This expansion is mediated by an increase in adipocyte numbers and/or enlargement of their size, by infiltration of immune cells, such as macrophages [3], into the adipose tissue, and by dysregulation of extracellular matrix remodelling in fat tissue [4]. Sustained obesity as well as chronic inflammation determines abnormal secretion of adipokines and myokines, excessive lipid storage, local hypoxia, and fibrosis [5].

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