Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

Abstract

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

Keywords: adipose tissue; ethnicity; metabolic risks; obesity; oxidative stress.

Figure 1

Schematic representation of oxidative stress drivers and metabolic consequences on adipose tissue (AT) function and whole-body metabolism. Obesity or overnutrition may result in nutrients overflow to AT, resulting in adipocyte hypertrophy and AT hypoxia which might induce an oxidative stress state in the tissue. Systemic inflammation, as well as behavioral factors, may also contribute to the disruption of the redox equilibrium of AT. As a result, the activation of stress signaling pathways contribute to increasing autophagy and apoptosis, dysregulated adipokine secretion and AT inflammation. The resulting functional alterations may further impair AT function by causing an increased attraction, infiltration and activation of immune cells and increased AT inflammation, creating a vicious cycle between AT oxidative stress and inflammation, and leading to whole-body metabolic dysfunction. These mechanisms might be influenced by ethnicity-related modulators.

Figure 2

Oxidative stress: an imbalance between reactive oxygen species (ROS) production and antioxidant defenses. ROS are generated during cellular metabolism when the chemical reduction of oxygen forms unstable free radicals. Several molecule types including lipids, proteins or nucleic acids can be oxidized or nitrated, and the resultant product, when accumulated in cells over time become harmful, affecting cell signaling pathways and tissue function. Physiological levels of ROS are conserved by the action of antioxidants, maintaining a redox balance in cells.

Figure 3

Adipose tissue expandability: proposed mechanisms whereby impaired adipogenesis during AT expansion may link oxidative stress to insulin resistance (IR). The most accepted mechanisms implicated in the impairment of AT function during excess fat accumulation include impaired adipogenesis and adipocyte hypertrophy, followed by increased FFAs release and ectopic fat deposition, dysregulation of adipokine secretion, increased hypoxia and AT cellular stresses such as oxidative stress. These mechanisms contribute in concert to the establishment of a pro-inflammatory state in AT, interfering with the insulin signaling pathway and leading to peripheral and systemic insulin resistance. Via elevated ROS production, oxidative stress may further impair AT function initiating a vicious cycle between AT expansion and IR. Abbreviations: ER: endoplasmic reticulum; FFA: free fatty acids; UPR: unfolded protein response; JNK: Jun N-terminal kinase; NFkB: nuclear factor-kappa B.