Browsing by Author "Coe, Christopher L."

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    Association between serum sphingolipids and eudaimonic well-being in white US adults
    (2021) Berkowitz, Loni; Henriquez, Marcela P.; Salazar, Cristian; Rojas, Eric; Echeverria, Guadalupe; Love, Gayle D.; Rigotti, Attilio; Coe, Christopher L.; Ryff, Carol D.
    Emerging research has linked psychological well-being with many physiological markers as well as morbidity and mortality. In this analysis, the relationship between components of eudaimonic well-being and serum sphingolipids levels was investigated using data from a large national survey of middle-aged American adults (Midlife in the United States). Health behaviors (i.e., diet, exercise, and sleep) were also examined as potential mediators of these relationships. Serum levels of total ceramides-the main molecular class of sphingolipids previously associated with several disease conditions-were inversely linked with environmental mastery. In addition, significant correlations were found between specific ceramide, dihydroceramide, and hexosylceramides species with environmental mastery, purpose in life, and self-acceptance. Using hierarchical regression and mediation analyses, health behaviors appeared to mediate these associations. However, the link between ceramides and environmental mastery was partially independent of health behaviors, suggesting the role of additional mediating factors. These findings point to sphingolipid metabolism as a novel pathway of health benefits associated with psychological well-being. In particular, having a sense of environmental mastery may promote restorative behaviors and benefit health via improved blood sphingolipid profiles.
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    Lipidomic Signature of Healthy Diet Adherence and Its Association with Cardiometabolic Risk in American Adults
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024) Berkowitz, Loni; Echeverría, Guadalupe; Salazar, Cristian; Faúndez, Cristian; Coe, Christopher L.; Ryff, Carol; Rigotti, Attilio
    The aim of this study was to identify the blood lipidomic profile associated with a healthy eating pattern in a middle-aged US population sample and to determine its relationship with metabolic disorders and cardiovascular risk (CVR). Self-reported information about diet and blood samples were obtained from 2114 adult participants in the Midlife in the United States study (MIDUS). Food intake data were used to design a Healthy Diet Index (MIDUS-HEI) and to evaluate the predictive value by examining its association with health variables. The associated lipid signature (HEI-LS) was constructed using Lasso regression, from lipidomic data (LC/MS). Associations between HEI-LS, cardiometabolic biomarkers, and estimated CVR were assessed using multiple linear regression. MIDUS-HEI score was a robust indicator of dietary quality and inversely associated with body mass index (p < 0.001) and metabolic syndrome (p = 0.012). A lipidomic signature comprising 57 distinct lipid species was highly correlated with the MIDUS-HEI score (r = 0.39, p < 10⁻16). It was characterized by lower levels of saturated fatty acid and adrenic acid (n-6) and higher levels of docosahexaenoic acid (n-3). Healthier HEI-LS scores were strongly associated with better cardiometabolic indicators and lower estimated CVR (OR 0.89 CI 95% 0.87–0.91). The MIDUS-HEI effectively assessed dietary quality, confirming the link between poor diet quality and metabolic disorders in American population. Lipidomic profiling offered an objective assessment of dietary patterns and provided insights into the relationship between diet quality, metabolic responses, and CVR. This approach supports precision nutrition strategies for at-risk populations.
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    Race and sex differences in HDL peroxide content among American adults with and without type 2 diabetes
    (2022) Flaherty, Shelby M.; Wood, Elizabeth K.; Ryff, Carol D.; Love, Gayle D.; Kelesidis, Theodoros; Berkowitz Fiebich, Loni; Echeverría Errázuriz, Guadalupe; Rivera Vega, Katherine Solange; Rigotti Rivera, Attilio; Coe, Christopher L.
    Background: High-density lipoprotein (HDL) plays a critical role in protection against atherosclerosic and cardiovascular disease (ASCVD). In addition to contributing to clearing excess vascular cholesterol, HDL particles exhibit antioxidative functions, helping to attenuate adverse effects of oxidized low-density lipoproteins. However, these beneficial properties can be undermined by oxidative stress, inflammation, and unhealthy lifestyles and diet, as well as influenced by race and sex. Thus, when assessing cardiovascular risk, it is important to consider multifactorial aspects of HDL, including antioxidant activity rather than just total amount and type of HDL-cholesterol (HDL-C) particles. Because prior research showed HDL peroxide content (HDLperox) can be inversely associated with normal anti-oxidant HDL activity, elevated HDLperox may serve as a bioindicator of HDL dysfunction. Methods: In this study, data from a large national cohort of Americans was utilized to determine the impact of sex, race, and diabetes status on HDLperox in middle-aged and older adults. A previously developed cell-free fluorometric method was utilized to quantify HDLperox in serum depleted of apo-B containing lipoproteins. Results: In keeping with predictions, white men and diabetics exhibited HDLperox in the atypical upper range, suggestive of less functional HDL. White men had higher HDLperox levels than African American males (13.46 ± 6.10 vs. 10.88 ± 5.81, p < .001). There was also a significant main effect of type 2 diabetes (F(1,1901) = 14.9, p < .0001). Overall, African Americans evinced lower HDLperox levels, despite more obesity (10.3 ± 4.7 vs.11.81 ± 5.66 for Whites) suggesting that other aspects of lipid metabolism and psychosocial factors account for the higher prevalence of ASCVD in African Americans. Conclusion: This research helps to provide a more comprehensive understanding of HDL function in a racially and metabolically diverse adult population. HDLperox content was significantly different in adults with type 2 diabetes, and distinctive in nondiabetic White males, and suggests other processes account for the higher prevalence of ASCVD among African Americans.
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    Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies
    (Springer Nature, 2024) Berkowitz Fiebich Loni; Razquin, Cristina; Salazar Vilches, Cristian Javier; Biancardi Roman, Fiorella Carinna; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Corella, Dolores; Coe, Christopher L.; Ryff, Carol D.; Ruiz-Canela, Miguel; Salas-Salvado, Jordi; Wang, Daniel; Hu, Frank B.; Deik, Amy; Martínez-González, Miguel A.; Rigotti Rivera, Attilio Gianpietro
    Background Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk. Methods Cross-sectional relationship between sphingolipid levels, insulin resistance, and T2D prevalence were evaluated in 2,072 American adults from MIDUS cohort. Prospectively, the association between sphingolipid species and the incidence of T2D was analyzed using a case-cohort design nested within the PREDIMED trial (250 cases and a random sample of 692 participants, with 3.8 years of median follow-up). Circulating levels of sphingolipid species in both populations were measured using LC/MS. Hazard ratios were estimated with weighted Cox regression models using Barlow weights. Results In American adults, only CER18:0 and CER22:0 were linked to insulin resistance and a higher prevalence of T2D. Conversely, three lactosylceramides (LCER 14:0, 16:0, and 24:1) showed a strong inverse relationship with both insulin resistance and T2D. These findings led to development of two sphingolipid scores. In the prospective analysis, these scores consistently predicted a reduced risk of T2D incidence in PREDIMED (HR: 0.64, 95% CI 0.44 to 0.94 and 0.58, 0.40 to 0.85 respectively) between extreme quartiles, with 5-year absolute risk differences of 9.6% (95% CI: 0.3–20.5%) and 11.4% (1.0–21.6%). They were validated in the same trial with samples obtained after 1 year of follow-up. Conclusions Our findings support the potential usefulness of circulating sphingolipid profiles as novel biomarkers for T2D risk. Moreover, this study opens the door for future research on the predictive value and possible protective roles of lactosylceramides in T2D. Graphical abstract