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Metabolic impairments associated with type 2 diabetes, including insulin resistance and loss of glycaemic control, disproportionately impact the elderly. Lifestyle interventions, such as manipulation of dietary fat quality (i.e. fatty acid (FA) composition), have been shown to favourably modulate metabolic health. Yet, whether or not chronic consumption of beneficial FAs can protect against metabolic derangements and disease risk during ageing is not well defined. We sought to evaluate whether long-term dietary supplementation of fish-, dairy- or echium-derived FAs to the average FA profile in a U.S. American diet may offset metabolic impairments in males and females during ageing. One-month-old CD-1® mice were fed isoenergetic, high-fat (40 %) diets with the fat content composed of either 100 % control fat blend (CO) or 70 % CO with 30 % fish oil, dairy fat or echium oil for 13 months. Every 3 months, parameters of glucose homoeostasis were evaluated via glucose and insulin tolerance tests. Glucose tolerance improved in males consuming a diet supplemented with fish oil or echium oil as ageing progressed, but not in females. Yet, females were more metabolically protected than males regardless of age. Additionally, Spearman correlations were performed between indices of glucose homoeostasis and previously reported measurements of diet-derived FA content in tissues and colonic bacterial composition, which also revealed sex-specific associations. This study provides evidence that long-term dietary fat quality influences risk factors of metabolic diseases during ageing in a sex-dependent manner; thus, sex is a critical factor to be considered in future dietary strategies to mitigate type 2 diabetes risk.
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Diabetes Mellitus Tipo 2 , Grasas de la Dieta , Ratones , Masculino , Femenino , Animales , Aceites de Pescado , Suplementos Dietéticos , GlucosaRESUMEN
BACKGROUND: There is currently no consensus on which tissues are optimal for assessing specific diet-derived fatty acids (FAs) as biomarkers for long-term dietary studies. OBJECTIVES: This study measured the content of unique diet-derived FAs from dairy, echium, and fish in tissues (adipose, muscle, liver, erythrocyte membranes, and plasma phospholipids, cholesterol esters, triglycerides, and free fatty acids) after long-term feeding in CD-1 mice. METHODS: Beginning at weaning, mice (n = 10-11/sex/diet) were fed 1 of 4 diets (40% kcal/total energy) that only differed in FA composition: control fat blend (CON), reflecting the FA profile of the average US American diet, or CON supplemented with 30% of fish oil (FO), dairy fat (DF), or echium oil (EO). After 13 mo, tissues were collected to determine FAs via gas-liquid chromatography. Tissue FAs were analyzed via 2-factor ANOVA, and relationships between FA intake and tissue content were assessed with Spearman correlations. RESULTS: As anticipated, 20:5n-3 (ω-3) tissue content was ≤32-fold greater in FO- compared with CON-fed mice (P < 0.05). In addition, 20:5n-3 intake strongly correlated with its content in all tissues (ρ = 0.67-0.76; P < 0.05). Echium oil intake also influenced tissue FA content in mice as expected. For example, 18:3n-6 was ≤25-fold greater in adipose, muscle, and liver tissues of EO-fed compared with CON-fed mice (P < 0.05). Tissue content of FAs typically considered biomarkers of dairy fat intake (15:0, 16:1 t9, and 17:0) was often not greater in mice fed DF than other diet groups, although 18:2 c9, t11 content was ≤6-fold greater in tissues from DF-fed compared with CON-fed mice (P < 0.05). The content of dairy-derived FAs in blood fractions of females was up to 2-fold greater compared with males, whereas docosapentaenoic acid content was up to 1-fold greater in all blood fractions and in liver tissue of males compared with females (P < 0.05). In adipose, muscle, and liver tissue, the content of γ-linolenic acid and stearidonic acid was less than 1-fold greater in females than in males (P < 0.05). CONCLUSIONS: Our study indicates that the distribution of dietary FAs is tissue and sex dependent in aged CD-1 mice. Research using FA biomarkers should assess a combination of FA biomarkers to accurately validate patterns of FA intake and source.
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Ácidos Grasos , Aceites de Pescado , Animales , Biomarcadores , Dieta , Suplementos Dietéticos , Femenino , Masculino , RatonesRESUMEN
Reducing dairy fat intake is a common dietary guideline to limit energy and saturated fatty acid intake for the promotion of cardiometabolic health. However, research utilizing a holistic, food-based approach to assess the consumption of the fat found in dairy, a broad and diverse food group, may provide new insight into these guidelines. Dairy fat is comprised of a diverse assembly of fatty acids, triacylglycerols, sterols, and phospholipids, all uniquely packaged in a milk fat globule. The physical structure of this milk fat globule and its membrane is modified through different processing methods, resulting in distinctive dairy-fat matrices across each dairy product. The objectives of this narrative review were to first define and compare the dairy-fat matrix in terms of its unique composition, physical structure, and fat content across common dairy products (cow's milk, yogurt, cheese, and butter). With this information, we examined observational studies and randomized controlled trials published within the last 10 years (2013-2023) to assess the individual effects of the dairy-fat matrix in milk, yogurt, cheese, and butter on cardiometabolic health and evaluate the implications for nutrition guidance. Searches conducted on Ovid MEDLINE and PubMed® utilizing search terms for cardiometabolic health, both broadly and regarding specific disease outcomes and risk factors, yielded 59 studies that were analyzed and included in this review. Importantly, this review stratifies by both dairy product and fat content. Though the results were heterogeneous, most studies reported no association between intake of these individual regular-fat dairy products and cardiometabolic outcome measures, thus, the current body of evidence suggests that regular-fat dairy product consumption may be incorporated within overall healthy eating patterns. Research suggests that there may be a beneficial effect of regular-fat milk and yogurt intake on outcome measures related to body weight and composition, and an effect of regular-fat cheese intake on outcome measures related to blood lipids, but more research is necessary to define the directionality of this relationship. Lastly, we identify methodological research gaps and propose future research directions to bolster the current evidence base available for ascertaining the role of dairy fat in a healthy diet.
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There is an urgent need for global food systems transformation to realize a future where planetary health reaches its full potential. Paramount to this vision is the ability of stakeholders across sectors to understand how foods and dietary patterns impact food systems inclusive of all domains of sustainability-environmental, nutrition/health, economic and social. This article is a synopsis of presentations by 3 food systems experts to share the latest science in a session entitled "How do you measure sustainability? Opportunities for consistent and holistic metrics to support food systems transformation" at the American Society for Nutrition's 2023 annual conference. As summarized here, global population data showing widespread malnutrition underscore the important role of dietary diversity through a balance of plant- and animal-source foods to achieve nutritionally adequate diets and reduce risk of noncommunicable diseases. Yet, recent international audits of countries, companies, and organizations and their sustainability targets largely demonstrate an underrepresentation of robust nutrition/health metrics to support public nutrition and health progress. Addressing limitations in diet-sustainability modeling systems provides a viable opportunity to accurately reflect the important contributions and trade-offs of diets across all domains of sustainability to ultimately support evidence-based decision making in advancing healthy food systems.
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An emerging body of scientific evidence demonstrates that the food matrix-the interaction among nutrients, bioactive components, and physical structure of a food-can affect health in significant, unexpected ways beyond its individual nutrients. In particular, research suggests that consumption of dairy foods such as milk, yogurt, and cheese may affect human health in a matrix-dependent fashion. To disseminate and discuss the growing body of evidence surrounding the role of the dairy food matrix on cardiometabolic health, 3 expert researchers on the topic of the food matrix shared the latest science in a session entitled "Next-Level Health Solutions: The Magic of the Matrix" at the American Society for Nutrition's 2022 LIVE ONLINE Conference. This article is a summary of the literature presented and discussed during that session. A substantial body of literature demonstrates that full-fat dairy foods, particularly fermented dairy foods, may beneficially modulate cardiometabolic outcomes depending on an individual's health status. These findings have important implications for current authoritative dietary guidance that recommends the consumption of low-fat or fat-free dairy foods. Furthermore, this evidence may inform practical applications of harnessing dairy's unique profile of bioactives for health promotion and disease prevention at the individual and community levels.
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Background: As the COVID-19 pandemic continues, efforts to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding and transmission in both unvaccinated and vaccinated populations remain critical to informing public health policies and vaccine development. The utility of using real time RT-PCR cycle threshold values (CT values) as a proxy for infectious viral litres from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral litres derived from a focus-forming viral titre assay with SARS-CoV-2 RT-PCR CT values in both unvaccinated and vaccinated individuals infected with the Delta strain. Methods: Nasopharyngeal swabs positive for SARS-CoV-2 by RT-PCR with a CT value <27 collected from 26 June to 17 October 2021 at the University of Vermont Medical Center Clinical Laboratory for which vaccination records were available were included. Partially vaccinated and individuals <18 years of age were excluded. Infectious viral litres were determined using a micro-focus forming assay under BSL-3 containment. Results: In total, 119 specimens from 22 unvaccinated and 97 vaccinated individuals met all inclusion criteria and had sufficient residual volume to undergo viral titring. A negative correlation between RT-PCR CT values and viral litres was observed in both unvaccinated and vaccinated groups. No difference in mean CT value or viral titre was detected between vaccinated and unvaccinated groups. Viral litres did not change as a function of time since vaccination. Conclusions: Our results add to the growing body of knowledge regarding the correlation of SARS-CoV-2 RNA levels and levels of infectious virus. At similar CT values, vaccination does not appear to impact an individual's potential infectivity when infected with the Delta variant.
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Utilization of murine models remains a valuable tool in biomedical research, yet, disease phenotype of mice across studies can vary considerably. With advances in next generation sequencing, it is increasingly recognized that inconsistencies in host phenotype can be attributed, at least in part, to differences in gut bacterial composition. Research with inbred murine strains demonstrates that housing conditions play a significant role in variations of gut bacterial composition, however, few studies have assessed whether observed variation influences host phenotype in response to an intervention. Our study initially sought to examine the effects of a long-term (9-months) dietary intervention (i.e., diets with distinct fatty acid compositions) on the metabolic health, in particular glucose homeostasis, of genetically-outbred male and female CD-1 mice. Yet, mice were shipped from two different husbandry facilities of the same commercial vendor (Cohort A and B, respectively), and we observed throughout the study that diet, sex, and aging differentially influenced the metabolic phenotype of mice depending on their husbandry facility of origin. Examination of the colonic bacteria of mice revealed distinct bacterial compositions, including 23 differentially abundant genera and an enhanced alpha diversity in mice of Cohort B compared to Cohort A. We also observed that a distinct metabolic phenotype was linked with these differentially abundant bacteria and indices of alpha diversity. Our findings support that metabolic phenotypic variation of mice of the same strain but shipped from different husbandry facilities may be influenced by their colonic bacterial community structure. Our work is an important precautionary note for future research of metabolic diseases via mouse models, particularly those that seek to examine factors such diet, sex, and aging.
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Bacterias/clasificación , Dieta/efectos adversos , Heces/microbiología , Glucosa/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ratones Endogámicos/genética , Crianza de Animales Domésticos , Animales , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Modelos Animales , Fenotipo , Filogenia , Análisis de Secuencia de ADNRESUMEN
The fatty acid (FA) composition and content of whole milk (3.25% fat) from organic, omega-3 (n-3) FA fortified, and conventional retail brands available in the northeastern U.S. were assessed monthly via gas chromatography. Among the retail labels, organic milk stood out as it contained a distinct and more healthful FA profile, consistently comprising a higher content of unique bioactive FAs (short-chain FAs, odd- and branched-chain FAs, vaccenic acid, and conjugated linoleic acids) per serving, particularly during the warm season. The total content of saturated FAs did not differ by retail label. While organic and n-3 fortified milk contained a similar content of total n-3 FAs, the proportion of individual n-3 FAs differed significantly (organic milk: 18:3 n-3; n-3 fortified milk: 20:6 n-3) as a result of the production system and process, respectively. Overall, per serving, the FA profile of organic milk may provide added nutritional and health benefits.
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Ácidos Grasos/análisis , Leche/química , Alimentación Animal , Animales , Bovinos , Cromatografía de Gases , Dieta , Suplementos Dietéticos/análisis , Ácidos Grasos Omega-3/análisis , Femenino , Alimentos Orgánicos , Ácidos Linoleicos Conjugados/análisis , New England , Evaluación Nutricional , Ácidos Oléicos/análisis , Estaciones del AñoRESUMEN
Dairy fat and its fatty acids (FAs) have been shown to possess pro-health properties that can support health maintenance and disease prevention. In particular, branched-chain FAs (BCFAs), comprising approximately 2% of dairy fat, have recently been proposed as bioactive molecules contributing to the positive health effects associated with the consumption of full-fat dairy products. This narrative review evaluates human trials assessing the relationship between BCFAs and metabolic risk factors, while potential underlying biological mechanisms of BCFAs are explored through discussion of studies in animals and cell lines. In addition, this review details the biosynthetic pathway of BCFAs as well as the content and composition of BCFAs in common retail dairy products. Research performed with in vitro models demonstrates the potent, structure-specific properties of BCFAs to protect against inflammation, cancers, and metabolic disorders. Yet, human trials assessing the effect of BCFAs on disease risk are surprisingly scarce, and to our knowledge, no research has investigated the specific role of dietary BCFAs. Thus, our review highlights the critical need for scientific inquiry regarding dairy-derived BCFAs, and the influence of this overlooked FA class on human health.
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Productos Lácteos/análisis , Ácidos Grasos/química , Ácidos Grasos/farmacología , Leche/química , Animales , Ácidos Grasos/administración & dosificación , Ácidos Grasos/metabolismo , HumanosRESUMEN
Evidence suggests that sex influences the effect of diet on the gut bacterial composition, yet, no studies have been performed assessing dietary fatty acid composition (i.e., fat quality) in this context. This study examined the effect of dietary fat quality on colonic bacterial composition in an aged, genetically-diverse mouse population. CD-1 mice were fed isoenergetic diets consisting of (1) control fat (CO; "Western-style" fat blend), (2) CO supplemented with 30% fish oil, (3) CO supplemented with 30% dairy fat, or (4) CO supplemented with 30% echium oil. Fecal samples were collected at mid-life and aged (reproductively senescent) time points. Overall, the abundance of Bacteroidetes was greater in mice fed echium oil compared to mice fed the control fat. Examination of colonic bacterial relative abundance also revealed sex differences, with 73 bacterial taxa being differentially expressed in males and females. Notably, results showed a strong interactive effect among the diet, sex, and age of mice which influenced colonic bacterial relative abundance and alpha diversity. In males, supplementation of the diet with dairy fat or echium oil caused the abundance of Bacteroidetes and Bacteroides to change with age. Additionally, supplementation of the diet with fish oil induced sex-dependent changes in the alpha diversity of aged mice compared to mid-life. This work supports that sex is a critical factor in colonic bacterial composition of an aged, genetically-heterogenous population. Moreover, this study establishes that the effectiveness of dietary interventions for health maintenance and disease prevention via direct or indirect manipulation of the gut microbiota is likely dependent on an individual's sex, age, and genetic background.
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Colon/microbiología , Grasas de la Dieta/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Factores de Edad , Animales , Bacteroides/efectos de los fármacos , Bacteroides/crecimiento & desarrollo , Femenino , Aceites de Pescado/farmacología , Masculino , Ratones , Aceites de Plantas/farmacología , Factores SexualesRESUMEN
Lifestyle is a key modifiable risk factor involved in the manifestation of metabolic syndrome and, in particular, diet plays a pivotal role in its prevention and development. Current dietary guidelines discourage the consumption of saturated fat and dietary sources rich in saturated fat, such as dairy products, despite data suggesting that full-fat dairy consumption is protective against metabolic syndrome. This narrative review assessed the recent epidemiological and clinical research that examined the consumption of dairy-derived saturated fatty acids (SFA) on metabolic syndrome risk. In addition, this review evaluated studies of individual SFA to gain insight into the potential mechanisms at play with intake of a diet enriched with these dairy-derived fatty acids. This work underscores that SFA are a heterogenous class of fatty acids that can differ considerably in their biological activity within the body depending on their length and specific chemical structure. In summary, previous work on the impact of dairy-derived SFA consumption on disease risk suggests that there is currently insufficient evidence to support current dietary guidelines which consolidate all dietary SFA into a single group of nutrients whose consumption should be reduced, regardless of dietary source, food matrix, and composition.
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Productos Lácteos/análisis , Dieta/efectos adversos , Grasas de la Dieta/análisis , Ácidos Grasos/análisis , Síndrome Metabólico/etiología , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
PURPOSE: The prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) remains poor, and novel therapies are needed. The proteasome pathway represents a potential therapeutic target. A phase I trial of the second-generation proteasome inhibitor ixazomib in combination with MEC (mitoxantrone, etoposide, and cytarabine) was conducted in patients with R/R AML. PATIENTS AND METHODS: Dose escalation of ixazomib was performed using a standard 3 × 3 design. Gene-expression profiling was performed on pretreatment and posttreatment bone marrow or blood samples. RESULTS: The maximum tolerated dose of ixazomib in combination with MEC was 1.0 mg. The dose limiting toxicity was thrombocytopenia. Despite a poor risk population, the response rate [complete remission (CR)/CR with incomplete count recovery (CRi)] was encouraging at 53%. Gene-expression analysis identified two genes, IFI30 (γ-interferon inducible lysosomal thiol reductase) and RORα (retinoic orphan receptor A), which were significantly differentially expressed between responding and resistant patients and could classify CR. CONCLUSIONS: These results are encouraging, but a randomized trial is needed to address whether the addition of ixazomib to MEC improves outcome. Gene-expression profiling also helped us identify predictors of response and potentially novel therapeutic targets.