Oxidative stress is associated with suspected non‐alcoholic fatty liver disease and all‐cause mortality in the general population

Abstract

Background & Aims Non‐alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD. Methods Protein‐adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End‐Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ≥ 60) and Hepatic Steatosis Index (HSI > 36). Results Protein‐adjusted serum free thiols were significantly reduced in subjects with FLI ≥ 60 (n = 1651). In multivariable logistic regression analyses, protein‐adjusted serum free thiols were associated with NAFLD (FLI ≥ 60) (OR per doubling of concentration: 0.78 [95% CI 0.64‐0.96], P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65‐0.99], P = .04). This association lost its significance (OR 0.94 [95% CI 0.73‐1.21], P = .65) after additional adjustment for high‐sensitive C‐reactive protein. Stratified analyses showed significantly differential associations of protein‐adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein‐adjusted serum free thiols were significantly associated with the risk of all‐cause mortality in subjects with NAFLD (FLI ≥ 60) (HR 0.27 [95% CI 0.17‐0.45], P < .001). Conclusion Protein‐adjusted serum free thiol levels are reduced and significantly associated with all‐cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all‐cause mortality in the general population.

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population

“…In the present study, we observed independent associations between serum free thiols and systolic blood pressure, hs-CRP and eGFR among premenopausal females, and with age, BMI, eGFR, and hemoglobin levels among postmenopausal females. These associations corroborate the findings of previous studies that examined serum free thiols in both healthy and diseased population cohorts ( 8 , 12 , 13 , 37 , 38 ). All these associations reflect a strong association between reduced systemic oxidative stress (i.e., lower levels of serum free thiols) and a favorable cardiovascular risk profile (e.g., lower age, BMI, blood pressure and hs-CRP, and higher eGFR and hemoglobin levels).…”

Young and Undamaged rMSA Improves the Healthspan and Lifespan of Mice

“…It was well documented that the four parameters of free thiol, carbonyl, AGE, and hcy are closely related to various diseases such as diabetes mellitus, cardiovascular diseases, adiposity, and Alzheimer's disease [10,23,29,[36][37][38]. We discovered that longevity is intimately related to these four major parameters, based on which we defined the status of exogenous rMSA as "young and undamaged".…”

Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy

“…NAFLD patients also show increased levels of peroxidised lipids, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which are often used as biomarkers of lipid peroxidation in clinical practice [9]. Moreover, a recent report suggests that reduced levels of free thiol plasma levels can be considered as a global marker of the systemic load of reactive species and can be used as a biomarker for NAFLD [39].…”