Chile is currently experiencing a progressive epidemiological transition towards chronic diseases. In this country, >50% of annual deaths are attributed to cardiovascular disease and cancer. Moreover, health surveys have shown high prevalence of obesity, diabetes, hypertension, and elevated cardiovascular disease risk. In addition, mental health issues are also frequent among Chilean adults. On the other hand, the agri-food system contributes to 21–37% of greenhouse gases emissions worldwide. Overall, current health and food chain situation calls out for design and implementation of evidence-based feasible and effective nutritional interventions needed to promote physical and mental health along with addressing food sustainability in Chile. Nowadays, the Mediterranean diet is recognized as one of the healthiest dietary patterns based on observational and interventional studies linked to a wide variety of health outcomes. However, a Mediterranean lifestyle goes well beyond food intake: it includes promotion of psychosocial resources, community life as well as cultural traditions. Indeed, Mediterranean lifestyle is a true modus vivendi that integrally promotes physical, mental, and social well-being. In addition, the Mediterranean diet stands out for its environmental sustainability because it is characterized mainly as a plant-based dietary pattern with low carbon and water footprints. Remarkably, Central Chile has a Mediterranean-like setting with plant and animal food production and availability patterns comparable to those present in countries located around the Mediterranean Sea. Therefore, this article reviews how promotion of Mediterranean lifestyle adherence in Chile offers great potential for management of the ongoing epidemiological transition to chronic diseases as well to promote psychological well-being within a unique food system and dietary sustainability vision for this Latin American country.

Background: Sphingolipids are components of cell membrane structure, but also circulate in serum and are essential mediators of many cellular functions. While ceramides have been proposed previously as a useful biomarker for cardiometabolic disease, the involvement of other sphingolipids is still controversial. The aim of this study was to investigate the cross-sectional association between blood sphingolipidomic profiles and metabolic syndrome (MetS) as well as other atherosclerotic risk factors in a large population-based study in the U.S.Methods: Clinical data and serum sphingolipidomic profiling from 2,063 subjects who participated in the biomarker project of the Midlife in the United States (MIDUS) study were used.Results: Consistent with previous reports, we found a positive association between most ceramide levels and obesity, atherogenic dyslipidemia, impaired glucose metabolism, and MetS prevalence. In contrast, most simple β-glycosphingolipids (i.e., hexosylceramides and lactosylceramides) were inversely associated with dysmetabolic biomarkers. However, this latter sphingolipid class showed a positive link with inflammatory and vascular damage-associated biomarkers in subjects with MetS. Through metabolic network analysis, we found that the relationship between ceramides and simple β-glycosphingolipids differed significantly not only according to MetS status, but also with respect to the participants' C-reactive protein levels.Conclusion: Our findings suggest that a comprehensive sphingolipid profile is more informative about MetS than ceramides alone, and it may reveal new insights into the pathophysiology and further diabetic vs. cardiovascular risk in patients with MetS.

Metabolic syndrome (MetS) is a multicomponent risk condition that reflects the clustering of individual cardiometabolic risk factors related to abdominal obesity and insulin resistance. MetS increases the risk for cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM). However, there still is not total clinical consensus about the definition of MetS, and its pathophysiology seems to be heterogeneous. Moreover, it remains unclear whether MetS is a single syndrome or a set of diverse clinical conditions conferring different metabolic and cardiovascular risks. Indeed, traditional biomarkers alone do not explain well such heterogeneity or the risk of associated diseases. There is thus a need to identify additional biomarkers that may contribute to a better understanding of MetS, along with more accurate prognosis of its various chronic disease risks. To fulfill this need, omics technologies may offer new insights into associations between sphingolipids and cardiometabolic diseases. Particularly, ceramides –the most widely studied sphingolipid class– have been shown to play a causative role in both T2DM and CVD. However, the involvement of simple glycosphingolipids remains controversial. This review focuses on the current understanding of MetS heterogeneity and discuss recent findings to address how sphingolipid profiling can be applied to better characterize MetS-associated risks.

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

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.

High sense of purpose in life, a fundamental domain of eudaimonic well-being, has been consistently associated with lower risk for various obesity-related chronic diseases. Although this psychological feature correlates with some health behaviors as potential mediators, its association with healthy eating remains less explored. In addition, studies of these psycho-behavioral and health relationships in the South American population are lacking. This research sought to assess: (1) the cross-sectional association between self-reported purpose in life and overall healthy eating patterns, and (2) healthy food intake as a potential mediator of the inverse relationship between purpose in life and waist circumference. Data collected of 2060 US adults from the MIDUS study (5 ± 12 years, 55% women, mostly white people, and 42.5% obese) and 223 Chilean adults from the CHILEMED study (46.6 ± 9 years, 58.3% women, and 71.3% obese) were used. Anthropometric and sociodemographic variables were collected. Sense of purpose was assessed using the purpose in life subscale of the Ryff’s psychological well-being questionnaire. Diet quality was evaluated using healthy eating or low-fat diet indexes, according to extant food intake data in each cohort. The relationship between these variables was estimated by bivariate and multivariate linear regressions with appropriate adjustments. To establish whether a better diet quality could mediate a link of purpose in life and improved nutritional status (assessed by waist circumference), the association between these three variables was tested by bootstrapping-based mediation analysis. Our results show significant associations of sense of purpose with healthy eating and low-fat dietary patterns in both US and Chilean cohorts, respectively, even after adjusting for sociodemographic variables. According to the mediation analysis, the relationship between sense of purpose and waist circumference, as an indicator of abdominal obesity, appears to be partially mediated by healthier food intake in both samples. In conclusion, our findings suggest a plausible mechanism underlying the favorable impact of this well-being dimension on physical health. Given its protective effects, interventions aimed at increasing purpose in life may facilitate adherence to better dietary patterns, which, in turn, will reduce the risk for obesity-related chronic diseases.