Obesity Is Associated with Increased F2-Isoprostanes and IL-6 in Black Women

Abstract

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson’s correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10.

Evaluation of the relationship of cytokines concentrations tumor necrosis factor‐alpha, interleukin‐6, and C‐reactive protein in obese diabetics and obese non‐diabetics: A comparative study

“…Obesity is related to high IR and type 2 diabetes 21 ; many studies show that remodeling adipose tissue in obese individuals triggers the release of pro-inflammatory cytokines and chemokines, which can lead to systemic inflammation and IR. 22,23,24,25 The average ± SD of HOMA-IR in the obese diabetics was higher than in obese non-diabetics with 3.81 ± 1.12 and 1.41 ± 1.13, respectively; this relationship is surprising and confirms that obesity is a risk factor for non-diabetic obesity to become diabetic. 26 In the overweight or adiposity, IR initially triggers compensatory mechanisms, resulting in insulin hypersecretion that temporarily keeps blood sugar levels under control.…”

“…So, the data showed a highly significant difference in the levels of HOMA‐IR in both groups. Obesity is related to high IR and type 2 diabetes 21 ; many studies show that remodeling adipose tissue in obese individuals triggers the release of pro‐inflammatory cytokines and chemokines, which can lead to systemic inflammation and IR 22,23,24,25 . The average ± SD of HOMA‐IR in the obese diabetics was higher than in obese non‐diabetics with 3.81 ± 1.12 and 1.41 ± 1.13, respectively; this relationship is surprising and confirms that obesity is a risk factor for non‐diabetic obesity to become diabetic 26 .…”

Innovative assessment of lipid‐induced oxidative stress and inflammation in harvested human endothelial cells

“…Previous work has shown that African American individuals have a greater oxidative stress response to lipid infusion at doses of 0.8 mL/m 2 /min with heparin (200 U/hrs for 4 hrs) than in Whites (Lopes et al., 2003), which is confirmed by plasma levels of the oxidative stress biomarker F2‐isoprostane (Parsa et al., 2022; Saleem et al., 2023). However, a reliable protocol to measure dynamic changes in oxidative stress responses in human endothelial cells has yet to be developed.…”

Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy

“…7,9,11 This promotes oxidation of arachidonic acid and formation of IsoLGs (isolevuglandins) through the isoprostane endoperoxide pathway. 11,49 The IsoLGs covalently bind to lysines on proteins and form lipid-protein adducts that permanently alter protein structure and function. These altered proteins are recognized as foreign and induce an autoimmune-like state in hypertension.…”