scholarly journals Fatty acid metabolism and colon cancer protection by dietary methyl donor restriction

Metabolomics ◽  
2021 ◽  
Vol 17 (9) ◽  
Author(s):  
Oladimeji Aladelokun ◽  
Matthew Hanley ◽  
Jinjian Mu ◽  
John C. Giardina ◽  
Daniel W. Rosenberg ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Caloric Intake ◽  
Tumor Development ◽  
Positive Association ◽  
Plasma Metabolites ◽  
Methyl Donor ◽  
Cancer Suppression ◽  
Cancer Risk Reduction

Abstract Introduction A methyl donor depleted (MDD) diet dramatically suppresses intestinal tumor development in Apc-mutant mice, but the mechanism of this prevention is not entirely clear. Objectives We sought to gain insight into the mechanisms of cancer suppression by the MDD diet and to identify biomarkers of cancer risk reduction. Methods A plasma metabolomic analysis was performed on ApcΔ14/+ mice maintained on either a methyl donor sufficient (MDS) diet or the protective MDD diet. A group of MDS animals was also pair-fed with the MDD mice to normalize caloric intake, and another group was shifted from an MDD to MDS diet to determine the durability of the metabolic changes. Results In addition to the anticipated changes in folate one-carbon metabolites, plasma metabolites related to fatty acid metabolism were generally decreased by the MDD diet, including carnitine, acylcarnitines, and fatty acids. Some fatty acid selectivity was observed; the levels of cancer-promoting arachidonic acid and 2-hydroxyglutarate were decreased by the MDD diet, whereas eicosapentaenoic acid (EPA) levels were increased. Machine-learning elastic net analysis revealed a positive association between the fatty acid-related compounds azelate and 7-hydroxycholesterol and tumor development, and a negative correlation with succinate and β-sitosterol. Conclusion Methyl donor restriction causes dramatic changes in systemic fatty acid metabolism. Regulating fatty acid metabolism through methyl donor restriction favorably effects fatty acid profiles to achieve cancer protection.

scholarly journals Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High−Fat Diets

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3334
Author(s):  
Qianying Zuo ◽  
Karen L. Chen ◽  
Alicia Arredondo Arredondo Eve ◽  
Yu-Jeh Liu ◽  
Sung Hoon Kim ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Postmenopausal Women ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Health ◽  
Plasma Metabolites ◽  
Collagen Deposition ◽  
Metabolomics Data ◽  
Increased Risk

About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE−1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE−1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet−induced obesity (DIO) and leptin−deficient (ob/ob) mice. PaPE−1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE−1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE−1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE−1 and suggest that PaPE−1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.

scholarly journals Intrinsic Mitochondrial Nutrient Utilization May Underlie the Association of Metabolite Levels with BMIz and Insulin Resistance (FS03-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jennifer LaBarre ◽  
Karen Peterson ◽  
Wei Hao ◽  
Maureen Kachman ◽  
Lu Tang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Positive Association ◽  
Nutrient Utilization ◽  
Macronutrient Intake ◽  
C Peptide ◽  
Medium Chain ◽  
The Relationship

Abstract Objectives To identify metabolites associated with BMIz and insulin resistance (IR) among 108 girls and 98 boys aged 8–14 years. We sought evidence of whether altered mitochondrial nutrient utilization, as indicated by mitochondrial-derived metabolites, mediates the relationship between diet, IR and obesity. Methods Anthropometry, fasting untargeted-liquid chromatography/mass spectrometry-derived metabolites and C-Peptide, and semi-quantitative food frequency questionnaires were collected from adolescents in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort. Sex-stratified generalized linear models were used to identify metabolites that are marginally associated BMIz and HOMA C-peptide (HOMA-CP), accounting for puberty, age and muscle and fat area (FDR < 0.1). Assessed the relationship between energy-adjusted macronutrient intake with HOMA-CP and BMIz. Structural equation models coupled with hierarchical clustering identified clusters of metabolites that may mediate the relationship between macronutrient intake with BMIz and HOMA-CP. Results Stratification by sex demonstrated sex-specific associations with BMIz. Most notable were girl's positive association with diacylglycerols and boy's positive association with branched chain and aromatic amino acids, independent of HOMA-CP. Intermediates in fatty acid metabolism, including medium chain acylcarnitines (acylCN), were inversely associated with HOMA-CP. No direct relationship was observed between macronutrient intake with BMIz and IR. Using mediation analyses, fat intake is positively associated with BMIz and HOMA-CP through increases in levels of dicarboxylic fatty acids (DiC-FA), products of omega-oxidation. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of medium chain acylCN, products of β-oxidation. Conclusions Insulin resistance in children appears to be associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extra-mitochondrial fatty acid metabolism (DiC-FA), while higher carbohydrate intake appears to lead to accumulation of intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake. Funding Sources This work was supported by the NIEHS, EPA and NIDDK.

The Influence of Lactate and Dipyridamole on Myocardial Fatty Acid Metabolism in Man, Traced with 123l-17-lodo-heptadecanoic Acid

1990 ◽  
Vol 29 (01) ◽  
pp. 28-34 ◽  
Author(s):  
F. C. Visser ◽  
M. J. van Eenige ◽  
G. Westera ◽  
J. P. Roos ◽  
C. M. B. Duwel
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Time Activity ◽  
Time Value ◽  
Myocardial Fatty Acid Metabolism ◽  
Coronary Vasodilatation ◽  
Activity Curve ◽  
Normal Human ◽  
Plasma Lactate Level

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123l-17-iodoheptadecanoic acid (123l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123l-17-HDA scintigraphy of the heart.

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