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In Mexican Americans, metabolic conditions, such as obesity and type 2 diabetes (T2DM), are not necessarily associated with an increase in mortality; this is the so-called Hispanic paradox. In this cross-sectional analysis, we used a metabolomic analysis to look at the mechanisms behind the Hispanic paradox. To do this, we examined dietary intake and body mass index (BMI; kg/m2) in men and women and their effects on serum metabolomic fingerprints in 70 Mexican Americans (26 men, 44 women). Although having different BMI values, the participants had many similar anthropometric and biochemical parameters, such as systolic and diastolic blood pressure, total cholesterol, and LDL cholesterol, which supported the paradox in these subjects. Plasma metabolomic phenotypes were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS). A two-way ANOVA assessing sex, BMI, and the metabolome revealed 23 significant metabolites, such as 2-pyrrolidinone (p = 0.007), TMAO (p = 0.014), 2-aminoadipic acid (p = 0.019), and kynurenine (p = 0.032). Pathway and enrichment analyses discovered several significant metabolic pathways between men and women, including lysine degradation, tyrosine metabolism, and branch-chained amino acid (BCAA) degradation and biosynthesis. A log-transformed OPLS-DA model was employed and demonstrated a difference due to BMI in the metabolomes of both sexes. When stratified for caloric intake ( 2200 kcal/d), a separate OPLS-DA model showed clear separation in men, while females remained relatively unchanged. After accounting for caloric intake and BMI status, the female metabolome showed substantial resistance to alteration. Therefore, we provide a better understanding of the Mexican-American metabolome, which may help demonstrate how this population—particularly women—possesses a longer life expectancy despite several comorbidities, and reveal the underlying mechanisms of the Hispanic paradox.

Breast cancer (BC) is a heterogeneous malignancy that is responsible for a great portion of female cancer cases and cancer-related deaths in the United States. In comparison to other major BC subtypes, triple negative breast cancer (TNBC) presents with a relatively low survival rate and a high rate of metastasis. This has led to a strong, though largely unmet, need for more sensitive and specific methods of early-stage TNBC (ES-TNBC) detection to combat its high-grade pathology and relatively low survival rate. The current study employs a liquid chromatography-tandem mass spectrometry assay capable of targeted, highly specific, and sensitive detection of lipids to propose two diagnostic biomarker panels for TNBC/ES-TNBC. Using this approach, 110 lipids were reliably detected in 166 human plasma samples, 45 controls, and 121 BC (96 non-TNBC and 25 TNBC) subjects. Univariate and multivariate analyses allowed the construction and application of a 19-lipid biomarker panel capable of distinguishing TNBC (and ES-TNBC) from controls, as well as a 5-lipid biomarker panel capable of differentiating TNBC from non-TNBC and ES-TNBC from ES-non-TNBC. Receiver operating characteristic curves with notable classification performances were generated from the biomarker panels according to their orthogonal partial least-squares discrimination analysis models. TNBC was distinguished from controls with an area under the receiving operating characteristic curve (AUROC) = 0.93, sensitivity = 0.96, and specificity = 0.76 and ES-TNBC from controls with an AUROC = 0.96, sensitivity = 0.95, and specificity = 0.89. TNBC was differentiated from non-TNBC with an AUROC = 0.88, sensitivity = 0.88, and specificity = 0.79 and ES-TNBC from ES-non-TNBC with an AUROC = 0.95, sensitivity = 0.95, and specificity = 0.87. A pathway enrichment analysis between TNBC and controls also revealed significant disturbances in choline metabolism, sphingolipid signaling, and glycerophospholipid metabolism. To the best of our knowledge, this is the first study to propose a diagnostic lipid biomarker panel for TNBC detection. All raw mass spectrometry data have been deposited to MassIVE (dataset identifier MSV000085324).

In Mexican Americans, metabolic conditions, such as obesity and type 2 diabetes (T2DM), are not necessarily associated with an increase in mortality, this is the so-called Hispanic paradox. In this cross-sectional analysis, we used a metabolomic analysis to look at the mechanisms behind the Hispanic paradox. To do this, we examined dietary intake and body mass index (BMI, kg/m2) in men and women and their effects on serum metabolomic fingerprints in 70 Mexican Americans (26 men, 44 women). Although having different BMI values, the participants had many similar anthropometric and biochemical parameters, such as systolic and diastolic blood pressure, total cholesterol, and LDL cholesterol, which supported the paradox in these subjects. Plasma metabolomic phenotypes were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS). A two-way ANOVA assessing sex, BMI, and the metabolome revealed 23 significant metabolites, such as 2-pyrrolidinone (p = 0.007), TMAO (p = 0.014), 2-aminoadipic acid (p = 0.019), and kynurenine (p = 0.032). Pathway and enrichment analyses discovered several significant metabolic pathways between men and women, including lysine degradation, tyrosine metabolism, and branch-chained amino acid (BCAA) degradation and biosynthesis. A log-transformed OPLS-DA model was employed and demonstrated a difference due to BMI in the metabolomes of both sexes. When stratified for caloric intake (&lt, 2200 kcal/d vs. &gt, 2200 kcal/d), a separate OPLS-DA model showed clear separation in men, while females remained relatively unchanged. After accounting for caloric intake and BMI status, the female metabolome showed substantial resistance to alteration. Therefore, we provide a better understanding of the Mexican-American metabolome, which may help demonstrate how this population—particularly women—possesses a longer life expectancy despite several comorbidities, and reveal the underlying mechanisms of the Hispanic paradox.