Dataset Information

Lipid peroxidation biomarkers associated with height and obesity measures in the opposite direction in women.

ABSTRACT:

Objective

This study aimed to investigate whether and how lipid peroxidation markers are associated with height and obesity measures.

Methods

In two independent samples of women (Study 1: n = 1,005; Study 2: n = 1,158), systemic levels of lipid peroxidation were assessed by urinary markers F₂ -isoprostanes (F₂ -IsoPs) and its major metabolite (F₂ -IsoP-M), with gas chromatography/negative ion chemical ionization mass spectrometry assays. Anthropometric parameters were directly measured and genetically estimated, and they were used in the primary analysis and in a Mendelian randomization analysis in relation to lipid peroxidation, respectively, with general linear models.

Results

After adjusting for potential confounders, it was found that measured adult height was inversely associated with levels of F₂ -IsoPs (β = -0.89, p < 0.001) and F₂ -IsoP-M (β = -0.71, p = 0.003), whereas obesity measures were positively associated with F₂ -IsoP-M (β = 1.81, p < 0.001 for BMI; and β = 0.77, p < 0.001 for waist circumference). Results were consistent between the two study samples. The opposite associations were further replicated when using genetically determined measures of height and obesity in the Mendelian randomization analysis. Moreover, analyses mutually adjusted for height and obesity measures suggested that these associations were independent of one another.

Conclusions

This study, for the first time, to our knowledge, reveals that a shared biological process (lipid peroxidation) is associated with both height and obesity measures but in the opposite direction.

SUBMITTER: Li M

PROVIDER: S-EPMC9556262 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Lipid peroxidation biomarkers associated with height and obesity measures in the opposite direction in women.

Li Mengjie M Zhao Yingya Y Dai Qi Q Milne Ginger G Long Jirong J Cai Qiuyin Q Chen Qingxia Q Zhang Xianglan X Lan Qing Q Rothman Nathaniel N Gao Yu-Tang YT Shu Xiao-Ou XO Zheng Wei W Yang Gong G

Obesity (Silver Spring, Md.) 20220426 6

<h4>Objective</h4>This study aimed to investigate whether and how lipid peroxidation markers are associated with height and obesity measures.<h4>Methods</h4>In two independent samples of women (Study 1: n = 1,005; Study 2: n = 1,158), systemic levels of lipid peroxidation were assessed by urinary markers F<sub>2</sub> -isoprostanes (F<sub>2</sub> -IsoPs) and its major metabolite (F<sub>2</sub> -IsoP-M), with gas chromatography/negative ion chemical ionization mass spectrometry assays. Anthropome ...[more]

PMID: 35471642

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Project description:Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome.

Project description:Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far. In this study, we aimed to further explore this association by investigating biological markers of DNA and lipid damage due to oxidation in a comprehensive approach over two study cohorts of postpartum women (study cohort I and study cohort II). The severity of CM experiences (maltreatment load) was assessed in both studies using the Childhood Trauma Questionnaire. In study cohort I (N = 30), we investigated whether CM was associated with higher levels of structural DNA damage in peripheral blood mononuclear cells (PBMC) by two methods that are highly sensitive for detecting nuclear DNA strand breaks (comet assay and γH2AX staining). In study cohort II (N = 117), we then assessed in a larger cohort, that was specifically controlled for potential confounders for oxidative stress measurements, two established serum and plasma biomarkers of oxidative stress, one representing oxidative DNA and RNA damage (8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine; 8-OH(d)G) and the other representing lipid peroxidation (8-isoprostane). In study cohort I, the analyses revealed no significant main effects of maltreatment load on cellular measures of nuclear DNA damage. The analyses of peripheral oxidative stress biomarkers in study cohort II revealed a significant main effect of maltreatment load on free 8-isoprostane plasma levels, but not on total 8-isprostane plasma levels and 8-OH(d)G serum levels. Taken together, by combining different methods and two study cohorts, we found no indications for higher oxidative DNA damages with higher maltreatment load in postpartum women. Further research is needed to investigate whether this increase in free 8-isoprostane is a marker for oxidative stress or whether it is instead functionally involved in ROS-related signaling pathways that potentially regulate inflammatory processes following a history of CM.

Dataset Information

Lipid peroxidation biomarkers associated with height and obesity measures in the opposite direction in women.

Objective

Methods

Results

Conclusions

Publications

Lipid peroxidation biomarkers associated with height and obesity measures in the opposite direction in women.

Similar Datasets

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