Lipid Peroxidation And Inflammatory Response Differentiate With Changes In Liver Fat Among Obese Latino Youth Following Lifestyle Intervention

Introduction: Lipid peroxidation and inflammation are pivotal pathological processes involved in the progression of NAFLD, a prelude to cardiovascular disease. Lifestyle intervention is the cornerstone approach for preventing cardiometabolic disease among high-risk populations, yet studies have not examined the mechanisms by which lifestyle intervention may mediate changes in liver fat in youth. Hypothesis: Lifestyle intervention will decrease hepatic fat fraction (HFF), tumor necrosis alpha (TNF)-α, and malondialdehyde (MDA)-protein adducts. Methods: Latino youth with obesity (n=26, age 13.9±1.3, BMI% 98.1±1.1) and prediabetes completed a 6-month lifestyle intervention that included nutrition education (1 d/wk) and physical activity (3 d/wk). HFF was measured by MRI before and after intervention. Fasting serum samples were collected for measurement of lipid peroxidation, measured by MDA-protein adducts, and inflammation, measured by TNF-α. Repeated measures ANOVA models were used to examine the effect of lifestyle intervention on HFF, MDA-protein adducts, and TNF-α. Data are presented as Mean±SE. Results: The intervention led to significant decreases in HFF (from 7.0±1.1% to 5.4±0.7%, p=0.027) and TNF-α (from 1.7±1.0 to 1.5±0.1 pg/mL, p=0.050), but not MDA-protein adducts (from 266.4±28.4 to 253.8±29.3 pmol/mL, p=0.105). However, there was significant heterogeneity in changes in HFF whereby those with the greatest response (n=14) decreased HFF by -44.0% while non-responders (n=12) increased HFF by 67.5%. HFF responders exhibited significantly greater reductions in MDA-protein adducts (from 256.2±39.4 to 228.1±40.0 pmol/mL, Δ-10.1%) compared to HFF non-responders (from 278.4±42.5 to 283.7±43.2 pmol/mL, Δ2.0%; p=0.023). TNF-α was reduced in HFF responders (from 1.8±0.2 to 1.5±0.1 pg/mL, Δ-17.8%) compared to HFF non-responders (from 1.5±0.2 to 1.5±0.1 pg/mL, Δ-4.4%) but was not significant (p=0.231). Conclusions: Reductions in HFF through lifestyle changes were associated with greater reductions in markers of lipid peroxidation, but not inflammation. The effect of lifestyle intervention on HFF may be mediated by markers that extend beyond traditional clinical risk factors among high-risk youth.