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BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for â¼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.
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Cardiolipinas , Ácido Linoleico , Masculino , Camundongos , Animais , Cardiolipinas/metabolismo , Mitocôndrias , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fígado/metabolismo , Dieta , Fosfolipídeos/metabolismo , Ácidos Linoleicos/metabolismo , RespiraçãoRESUMO
PURPOSE OF REVIEW: As heart disease and type 2 diabetes mellitus (T2DM) cases continue to rise, identifying lifestyle modifications to prevent cardiometabolic disease (CMD) is urgently needed. Clinical evidence consistently shows that higher dietary or biomarker levels of linoleic acid (LA; 18:2n6) reduce metabolic syndrome (Mets) and reduce the risk for CMD. Yet, dietary recommendations to include LA as part of a lifestyle plan with the goal of preventing CMD remain elusive. RECENT FINDINGS: Clinical interventions consistently show that dietary the addition of LA to the diet improves body composition, dyslipidemia, and insulin sensitivity while reducing systemic inflammation and fatty liver. These effects of LA position dietary LA-rich oils as a potential dietary strategy to aid in preventing CMD. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are cellular targets for many polyunsaturated fatty acids and oxylipin metabolites. PPAR activation can regulate dyslipidemia, insulin sensitivity, adipose biology, and inflammation, potentially explaining the plethora of effects of dietary LA on aspects of CMD. SUMMARY: Unraveling the cellular mechanism(s) of LA to impact PPAR activity may reset a false dogma that LA, as a member of the omega-6 fatty acid family, promotes inflammation in humans. In fact, LA appears to reduce inflammation and reduce risk for CMD.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Ácido Linoleico , Ácidos Graxos Ômega-6 , Receptores Ativados por Proliferador de Peroxissomo , Inflamação , Doenças Cardiovasculares/prevenção & controleRESUMO
The social-signal-transduction theory of depression asserts that people who experience ongoing interpersonal stressors and mount a greater inflammatory response to social stress are at higher risk for depression. The current study tested this theory in two adult samples. In Study 1, physically healthy adults (N = 76) who reported more frequent interpersonal tension had heightened depressive symptoms at Visit 2, but only if they had greater inflammatory reactivity to a marital conflict at Visit 1. Similarly, in Study 2, depressive symptoms increased among lonelier and less socially supported breast-cancer survivors (N = 79). This effect was most pronounced among participants with higher inflammatory reactivity to a social-evaluative stressor at Visit 1. In both studies, noninterpersonal stress did not interact with inflammatory reactivity to predict later depressive symptoms.
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Depressão , Estresse Psicológico , Adulto , Humanos , Estudos Longitudinais , Exacerbação dos SintomasRESUMO
Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.
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Senescência Celular , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Estresse Fisiológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Citocinas , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona , Masculino , Pessoa de Meia-IdadeRESUMO
Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p = 0.001), greater sleep quality (p = 0.001), fewer health-impairing behaviors (p = 0.02), and higher RBC omega-3 fatty acids (p = 0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.
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Promoção da Saúde , Gestantes , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Recém-Nascido , Estudos Longitudinais , Gravidez , Gestantes/psicologia , Autorrelato , Apoio SocialRESUMO
BACKGROUND: Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. OBJECTIVES: The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. METHODS: This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. RESULTS: The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (ß = 0.015, P = 0.01) and grip strength (ß = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. CONCLUSIONS: The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.
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Neoplasias da Mama , Ácidos Graxos Ômega-3 , Idoso , Estudos Transversais , Eritrócitos , Ácidos Graxos , Feminino , Força da Mão , HumanosRESUMO
The consumption of a processed foods diet (PD) enriched with refined carbohydrates, saturated fats, and lack of fiber has increased in recent decades and likely contributed to increased incidence of chronic disease and weight gain in humans. These diets have also been shown to negatively impact brain health and cognitive function in rodents, non-human primates, and humans, potentially through neuroimmune-related mechanisms. However, mechanisms by which PD impacts the aged brain are unknown. This gap in knowledge is critical, considering the aged brain has a heightened state of baseline inflammation, making it more susceptible to secondary challenges. Here, we showed that consumption of a PD, enriched with refined carbohydrate sources, for 28 days impaired hippocampal- and amygdalar-dependent memory function in aged (24 months), but not young (3 months) F344 × BN rats. These memory deficits were accompanied by increased expression of inflammatory genes, such as IL-1ß, CD11b, MHC class II, CD86, NLRP3, and complement component 3, in the hippocampus and amygdala of aged rats. Importantly, we also showed that when the same PD is supplemented with the omega-3 polyunsaturated fatty acid DHA, these memory deficits and inflammatory gene expression changes were ameliorated in aged rats, thus providing the first evidence that DHA supplementation can protect against memory deficits and inflammatory gene expression in aged rats fed a processed foods diet. Lastly, we showed that while PD consumption increased weight gain in both young and aged rats, this effect was exaggerated in aged rats. Aging was also associated with significant alterations in hypothalamic gene expression, with no impact by DHA on weight gain or hypothalamic gene expression. Together, our data provide novel insights regarding diet-brain interactions by showing that PD consumption impairs cognitive function likely through a neuroimmune mechanism and that dietary DHA can ameliorate this phenomenon.
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Disfunção Cognitiva , Ácidos Graxos Ômega-3 , Animais , Carboidratos , Disfunção Cognitiva/prevenção & controle , Dieta , Ácidos Docosa-Hexaenoicos , Expressão Gênica , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
Short-term (3-day) consumption of a high fat diet (HFD) rich in saturated fats is associated with a neuroinflammatory response and subsequent cognitive impairment in aged, but not young adult, male rats. This exaggerated effect in aged rats could be due to a "primed" microglial phenotype observed in the normal aging process in rodents in which aged microglia display a potentiated response to immune challenge. Here, we investigated the impact of HFD on microglial priming and lipid composition in the hippocampus and amygdala of young and aged rats. Furthermore, we investigated the microglial response to palmitate, the main saturated fatty acid (SFA) found in HFD that is proinflammatory. Our results indicate that HFD increased gene expression of microglial markers of activation indicative of microglial priming, including CD11b, MHCII, CX3CR1, and NLRP3, as well as the pro-inflammatory marker IL-1ß in both hippocampus and amygdala-derived microglia. Furthermore, HFD increased the concentration of SFAs and decreased the concentration of polyunsaturated fatty acids (PUFAs) in the hippocampus. We also observed a specific decrease in the anti-inflammatory PUFA docosahexaenoic acid (DHA) in the hippocampus and amygdala of aged rats. In a separate cohort of young and aged animals, isolated microglia from the hippocampus and amygdala exposed to palmitate in vitro induced an inflammatory gene expression profile mimicking the effects of HFD in vivo. These data suggest that palmitate may be a critical nutritional signal from the HFD that is directly involved in hippocampal and amygdalar inflammation. Interestingly, microglial activation markers were increased in response to HFD or palmitate in an age-independent manner, suggesting that HFD sensitivity of microglia, under these experimental conditions, is not the sole mediator of the exaggerated inflammatory response observed in whole tissue extracts from aged HFD-fed rats.
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Ácidos Graxos , Microglia , Tonsila do Cerebelo , Animais , Dieta Hiperlipídica , Hipocampo , Masculino , RatosRESUMO
The Western diet, characterized by high intake of saturated fat, sugar, and salt, is associated with elevated inflammation and chronic disease risk. Few studies have investigated molecular mechanisms linking diet and inflammation; however, a small number of randomized controlled trials suggest that consuming an anti-inflammatory diet (i.e., a primarily plant-based diet rich in monounsaturated fat and lean protein) decreases proinflammatory gene expression. The current study investigated the association between everyday diet and proinflammatory gene expression, as well as the extent to which central adiposity and social involvement modulate risk. Participants were healthy middle-aged and older adults (Nâ¯=â¯105) who completed a food frequency questionnaire and reported how many close social roles they have. Anthropometric measurements and blood samples also were collected; gene expression data were analyzed from LPS-stimulated peripheral blood mononuclear cells for interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. The inflammatory potential of each participant's diet was calculated using the Dietary Inflammatory Index (DII®). Participants with higher DII® scores, indicating a more proinflammatory diet, had greater IL-6 (bâ¯=â¯-0.02, SEâ¯=â¯0.008, pâ¯=â¯.01), IL-1ß (bâ¯=â¯-0.01, SEâ¯=â¯0.006, pâ¯=â¯.03), and TNF-α (bâ¯=â¯-0.01, SEâ¯=â¯0.005, pâ¯=â¯.04) gene expression if they had a smaller sagittal abdominal diameter (SAD); effects were not seen among those with higher SADs. Social involvement served a protective role, such that participants with smaller SADs had greater IL-6 (bâ¯=â¯0.01, SEâ¯=â¯0.004, pâ¯=â¯.049) and IL-1ß (bâ¯=â¯0.01, SEâ¯=â¯0.003, pâ¯=â¯.045) gene expression only if they had less social involvement; there was no effect of diet on gene expression among those who reported greater social participation. Results are the first to demonstrate a link between self-reported diet and proinflammatory gene expression. Importantly, the effect of diet on gene expression depended upon both body fat composition and social participation, both of which have previously been linked directly with proinflammatory gene expression and inflammation.
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Dieta Ocidental/psicologia , Inflamação/genética , Inflamação/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal/genética , Composição Corporal/fisiologia , Peso Corporal/genética , Peso Corporal/fisiologia , Dieta/psicologia , Dieta Ocidental/efeitos adversos , Gorduras na Dieta , Feminino , Expressão Gênica/genética , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Fatores de Risco , Isolamento Social/psicologia , Fator de Necrose Tumoral alfa/sangueRESUMO
PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.
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Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/complicações , Ácidos Graxos Ômega-3/administração & dosagem , Dor Musculoesquelética/dietoterapia , Adulto , Idoso , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobreviventes de Câncer , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/patologia , Estadiamento de Neoplasias , Projetos Piloto , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω-3PUFA with breast tissue LCω-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross-sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LCω-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω-3PUFA tertile had LCω-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω-3PUFA were similar in magnitude. No significant association was found for the shorter ω-3 PUFA, α-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte ω-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.
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Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Glândulas Mamárias Humanas/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Mamoplastia , Glândulas Mamárias Humanas/cirurgia , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Loneliness is strongly linked to poor health. Recent research suggests that appetite dysregulation provides one potential pathway through which loneliness and other forms of social disconnection influence health. Obesity may alter the link between loneliness and appetite-relevant hormones, one unexplored possibility. We examined the relationships between loneliness and both postmeal ghrelin and hunger, and tested whether these links differed for people with a higher versus lower body mass index (BMI; kg/m(2)). During this double-blind randomized crossover study, women (N=42) ate a high saturated fat meal at the beginning of one full-day visit and a high oleic sunflower oil meal at the beginning of the other. Loneliness was assessed once with a commonly used loneliness questionnaire. Ghrelin was sampled before the meal and postmeal at 2 and 7h. Self-reported hunger was measured before the meal, immediately postmeal, and then 2, 4, and 7h later. Lonelier women had larger postprandial ghrelin and hunger increases compared with less lonely women, but only among participants with a lower BMI. Loneliness and postprandial ghrelin and hunger were unrelated among participants with a higher BMI. These effects were consistent across both meals. These data suggest that ghrelin, an important appetite-regulation hormone, and hunger may link loneliness to weight gain and its corresponding negative health effects among non-obese people.
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Grelina/metabolismo , Fome/fisiologia , Solidão/psicologia , Período Pós-Prandial/fisiologia , Apetite/fisiologia , Índice de Massa Corporal , Peso Corporal , Neoplasias da Mama/psicologia , Estudos Cross-Over , Dieta Hiperlipídica , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Sobrepeso/psicologia , Inquéritos e Questionários , SobreviventesRESUMO
OBJECTIVE: Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems. METHODS: Participants (n = 138) from a parent randomized controlled trial were randomized to the placebo, 1.25 grams/d of omega-3, or 2.50 grams/d of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the randomized controlled trial. RESULTS: After adjustment for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory postsupplementation, as measured by immediate (b = -0.28, t (117) = -2.62, p = .010) and long-delay (b = -0.06, t (116) = -2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25- and 2.50-grams/d supplementation groups (all p values > .10). The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests (all p values > .32). CONCLUSION: These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the use of exploring novel interventions for treating episodic memory problems among lonely people. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00385723.
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Ácidos Graxos Ômega-3/uso terapêutico , Solidão/psicologia , Transtornos da Memória/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Inquéritos e QuestionáriosRESUMO
Introduction: Cardiometabolic diseases (CMD) are the leading causes of death for people living in the United States. Dietary strategies, such as restricting carbohydrate intake, are becoming popular strategies for improving health status. However, there is limited and often contradictory evidence on whether restricting carbohydrate intake is related to all-cause, CMD, or cardiovascular disease (CVD) mortality. Methods: The objective of the present study was to evaluate the association between restricted carbohydrate diets (<45%en) and mortality from all-causes, CMD, and CVD, stratified by fat amount and class. Data were acquired using the National Health and Nutrition Examination Survey (1999-2018) linked with mortality follow-up until December 31, 2019 from the Public-use Linked Mortality Files. Multivariable survey-weighted Cox proportional hazards models estimated hazard ratios for 7,958 adults (≥20 y) that consumed <45%en from carbohydrates and 27,930 adults that consumed 45-65%en from carbohydrates. Results: During the study period a total of 3,780 deaths occurred, including 1,048 from CMD and 1,007 from CVD, during a mean follow-up of 10.2 y. Compared to individuals that met carbohydrate recommendations (45-65%en), those that consumed carbohydrate restricted diets (<45%en) did not have significantly altered risk of mortality from all-causes (HR: 0.98; 95% CI: 0.87, 1.11), CMD (1.18; 0.95, 1.46), or CVD (1.20; 0.96, 1.49). These findings were maintained when the restricted carbohydrate diet group was stratified by intake of total fat, saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA). Discussion: Carbohydrate restriction (<45%en) was not associated with mortality from all-causes, CVD, or CMD. Greater efforts are needed to characterize the risk of mortality associated with varied degrees of carbohydrate restriction, e.g., low (<26%en) and high (>65%en) carbohydrate diets separately.
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BACKGROUND: Mischaracterization of dietary intake by patients and study participants is a common problem that presents challenges to clinical and public health approaches to improve diet quality, identify healthy eating patterns, and reduce the risk of chronic disease. OBJECTIVE: This study examined participants' self-reported adherence to low-carbohydrate and low-fat diets compared with their estimated adherence using up to 2 24-hour recalls. DESIGN: This cross-sectional study acquired data on dietary intake from respondents in the National Health and Nutrition Examination Survey, 2007-2018. PARTICIPANTS/SETTING: This study included 30 219 respondents aged 20 years and older who had complete and reliable dietary data and were not pregnant or breastfeeding. MAIN OUTCOME MEASURES: The main outcome was prevalence of self-reported and estimated adherence to low-carbohydrate or low-fat diet patterns. STATISTICAL ANALYSES PERFORMED: Self-reported adherence to low-carbohydrate or low-fat diets was evaluated using responses to questionnaires. Estimated adherence to these diets was assessed using data from up to 2 24-hour recalls and usual intake methodology developed by the National Cancer Institute. RESULTS: Of the 1.4% of participants who reported following a low-carbohydrate diet, estimated adherence (<26% energy from carbohydrates) using 24-hour recalls was 4.1%, whereas estimated adherence among those that did not report following a low-carbohydrate diet was <1% (P value for difference = .014). Of the 2.0% of participants who reported following a low-fat diet, estimated adherence (<30% energy from fat) was 23.0%, whereas estimated adherence among those who did not report following a low-fat diet was 17.8% (P value for difference = .048). CONCLUSIONS: This research demonstrates that most individuals mischaracterized their diet pattern when compared with up to 2 24-hour recalls. These findings emphasize the need for clinicians and public health professionals to be cautious when interpreting individuals' self-reported diet patterns, and should aim to collect more detailed dietary data when possible.
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BACKGROUND: This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan. METHODS: Peripheral blood was obtained from 96 study participants (Nâ =â 96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation. T cell aging mRNA markers were combined into an aging index, and the Horvath epigenetic clock algorithm was used to calculate epigenetic age based on DNA methylation status of over 500 loci. Participants also collected a stool sample from which the V4 region of the 16S rRNA gene was sequenced to derive the Shannon and Simpson diversity indices, and the total count of observed operational taxonomic units (richness). Models controlled for BMI, comorbidities, sex, dietary quality, smoking status, physical activity, and sleep quality. RESULTS: Lower microbiota richness was associated with higher T cell age based on mRNA markers, but when probing the region of significance, this relationship was only significant among adults 45 years and older (pâ =â .03). Lower Shannon diversity (pâ =â .05) and richness (pâ =â .07) marginally correlated with higher epigenetic age (ie, greater T cell DNA methylation). CONCLUSIONS: Gut microbiota complexity may correspond with the rate of T cell aging, especially in mid-to-late life. These results suggest an interplay between the gut microbiome and immunological aging that warrants further experimental work.
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Microbioma Gastrointestinal , Microbiota , Humanos , RNA Ribossômico 16S/genética , Senescência de Células T , RNA MensageiroRESUMO
OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.
Assuntos
Ácidos Graxos , Ácido Linoleico , Pancreatite Crônica , Humanos , Projetos Piloto , Pancreatite Crônica/sangue , Pancreatite Crônica/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Ácidos Graxos/sangue , Ácido Linoleico/sangue , Estudos de Casos e Controles , Lipogênese , Idoso , Ácido Palmítico/sangue , Ácido Oleico/sangue , Biomarcadores/sangueRESUMO
INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.