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1.
Am J Physiol Cell Physiol ; 326(4): C1027-C1033, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38314726

RESUMEN

This study examined the effect of exogenous ketone bodies (KB) on oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and glucose metabolism. The data were compared with the effects of endogenous ketonemia during both, a ketogenic diet or fasting. Eight healthy individuals [24.1 ± 2.5 yr, body mass index (BMI) 24.3 ± 3.1 kg/m2] participated in a crossover intervention study and were studied in a whole-room indirect calorimeter (WRIC) to assess macronutrient oxidation following four 24-h interventions: isocaloric controlled mixed diet (ISO), ISO supplemented with ketone salts (38.7 g of ß-hydroxybutyrate/day, EXO), isocaloric ketogenic diet (KETO), and total fasting (FAST). A physical activity level of 1.65 was obtained. In addition to plasma KB, 24-h C-peptide and KB excretion rates in the urine and postprandial glucose and insulin levels were measured. Although 24-h KB excretion increased in response to KETO and FAST, there was a modest increase in response to EXO only (P < 0.05). When compared with ISO, V̇o2 significantly increased in KETO (P < 0.01) and EXO (P < 0.001), whereas there was no difference in FAST. V̇co2 increased in EXO but decreased in KETO (both P < 0.01) and FAST (P < 0.001), resulting in 24-h respiratory exchange ratios (RER) of 0.828 ± 0.024 (ISO) and 0.811 ± 0.024 (EXO) (P < 0.05). In response to EXO there were no differences in basal and postprandial glucose and insulin levels, as well as in insulin sensitivity. When compared with ISO, EXO, and KETO, FAST increased homeostatic model assessment ß-cell function (HOMA-B) (all P < 0.05). In conclusion, at energy balance exogenous ketone salts decreased respiratory exchange ratio without affecting glucose tolerance.NEW & NOTEWORTHY Our findings revealed that during isocaloric nutrition, additional exogenous ketone salts increased V̇o2 and V̇co2 while lowering the respiratory exchange ratio (RER). Ketone salts had no effect on postprandial glucose metabolism.


Asunto(s)
Insulinas , Cetonas , Humanos , Voluntarios Sanos , Sales (Química) , Glucosa , Metabolismo Energético , Glucemia/metabolismo
2.
Cell Mol Life Sci ; 80(3): 59, 2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36749362

RESUMEN

BACKGROUND AND AIMS: Apolipoprotein E (APOE) is known for its role in lipid metabolism and its association with age-related disease pathology. The aim of the present work was to identify previously unknown functions of APOE based on the detection of novel APOE protein-protein interaction candidates. APPROACH AND RESULTS: APOE targeted replacement mice and transfected cultured hepatocytes expressing the human isoforms APOE3 and APOE4 were used. For 7 months, APOE3 and APOE4 mice were fed a high-fat and high-sugar diet to induce obesity, while a subgroup was subjected to 30% dietary restriction. Proteomic analysis of coimmunoprecipitation products from APOE mouse liver extracts revealed 28 APOE-interacting candidate proteins, including branched-chain alpha-keto acid dehydrogenase (BCKD) complex subunit alpha (BCKDHA) and voltage-dependent anion-selective channel 1 (VDAC1). The binding of APOE and BCKDHA was verified in situ by proximity ligation assay in cultured cells. The activity of the BCKD enzyme complex was significantly higher in obese APOE4 mice than in APOE3 mice, while the plasma levels of branched-chain amino acids and mTOR signalling proteins were not different. However, the protein-protein interaction with VDAC1 was strongly induced in APOE3 and APOE4 mice upon dietary restriction, suggesting a prominent role of APOE in mitochondrial function. CONCLUSIONS: The protein-protein interactions of APOE with BCKDHA and VDAC1 appear to be of physiological relevance and are modulated upon dietary restriction. Because these are mitochondrial proteins, it may be suggested that APOE is involved in mitochondria-related processes and adaptation to hepatic energy demands.


Asunto(s)
Apolipoproteína E4 , Proteómica , Ratones , Humanos , Animales , Apolipoproteína E4/metabolismo , Apolipoproteína E3/metabolismo , Apolipoproteínas E/metabolismo , Hígado/metabolismo , Células Cultivadas , Mitocondrias/metabolismo , Proteínas Portadoras/metabolismo , Ratones Transgénicos
3.
Int J Mol Sci ; 25(19)2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39408926

RESUMEN

As a component of circulating lipoproteins, APOE binds to cell surface receptors mediating lipoprotein metabolism and cholesterol transport. A growing body of evidence, including the identification of a broad variety of cellular proteins interacting with APOE, suggests additional independent functions. Investigating cellular localization and protein-protein interactions in cultured human hepatocytes, we aimed to contribute to the elucidation of hitherto unnoted cellular functions of APOE. We observed a strong accumulation of APOE in MAMs, equally evident for the two major isoforms APOE3 and APOE4. Using mass spectrometry proteome analyses, novel and previously noted APOE interactors were identified, including the mitochondrial proteins TOMM40, LONP1 and VDAC1. All three interactors were present in MAM fractions, which we think initially facilitates interactions with APOE. LONP1 is a protease with chaperone activity, which migrated to MAMs in response to ER stress, displaying a reinforced interaction with APOE. We therefore hypothesize that APOE may help in the unfolded protein response (UPR) by acting as a co-chaperone in cooperation with LONP1 at the interface of mitochondria and ER membranes. The interaction of APOE with the integral proteins TOMM40 and VDAC1 may point to the formation of bridging complexes connecting mitochondria with other organelles.


Asunto(s)
Apolipoproteínas E , Retículo Endoplásmico , Proteínas de Transporte de Membrana Mitocondrial , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Canal Aniónico 1 Dependiente del Voltaje , Humanos , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/genética , Apolipoproteínas E/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Proteasas ATP-Dependientes/metabolismo , Unión Proteica , Hepatocitos/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Respuesta de Proteína Desplegada
4.
J Nutr ; 153(5): 1524-1533, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36906150

RESUMEN

BACKGROUND: Elevated concentrations of ferritin seem to be detrimental to human health while being quite common in the elderly. Data on dietary, anthropometric, and metabolic correlates of circulating ferritin levels in the elderly are scant. OBJECTIVES: We aimed to identify a dietary pattern, anthropometric, and metabolic traits associated with plasma ferritin status in an elderly cohort (n = 460, 57% male, age: 66 ± 12 y) from Northern Germany. METHODS: Plasma ferritin levels were measured by immunoturbidimetry. Reduced rank regression (RRR) yielded a dietary pattern explaining 13% of the variation in circulating ferritin concentrations. Cross-sectional associations of anthropometric and metabolic traits with plasma ferritin concentrations were assessed using multivariable-adjusted linear regression analysis. Restricted cubic spline regression was used to identify nonlinear associations. RESULTS: The RRR pattern was characterized by a high intake of potatoes, certain vegetables, beef, pork, processed meat, fats (frying and animal fat), and beer and a low intake of snacks, representing elements of the traditional German diet. BMI, waist circumference, and CRP were directly, HDL cholesterol inversely, and age nonlinearly associated with plasma ferritin concentrations (all P < 0.05). After additional adjustment for CRP, only the association of ferritin with age remained statistically significant. CONCLUSION: Higher plasma ferritin concentrations were associated with a traditional German dietary pattern. The associations of ferritin with unfavorable anthropometric traits and low HDL cholesterol were rendered statistically nonsignificant upon additional adjustment for chronic systemic inflammation (measured as elevated biomarker of the measurement of inflammation (CRP)), suggesting that these associations were largely driven by the proinflammatory role of ferritin (an acute-phase reactant).


Asunto(s)
Dieta , Ferritinas , Animales , Bovinos , Humanos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Estudios Transversales , HDL-Colesterol , Inflamación
5.
Am J Nephrol ; 54(9-10): 425-433, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37231776

RESUMEN

INTRODUCTION: In chronic kidney disease, proteinuria increases urinary copper excretion, inducing oxidative tubular damage and worsening kidney function. We investigated whether this phenomenon occurred in kidney transplant recipients (KTRs). In addition, we studied the associations of urinary copper excretion with the biomarker of oxidative tubular damage urinary liver-type fatty-acid binding protein (u-LFABP) and death-censored graft failure. METHODS: This prospective cohort study was performed in the Netherlands between 2008 and 2017, including outpatient KTR with a functioning graft for longer than 1 year, who were extensively phenotyped at baseline. Twenty-four-hour urinary copper excretion was measured by inductively coupled plasma mass spectrometry. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (57% men, 53 ± 13 years, estimated glomerular filtration rate [eGFR] 52 ± 20 mL/min/1.73 m2), baseline median urinary copper excretion was 23.6 (interquartile range 11.3-15.9) µg/24 h. Urinary protein excretion was positively associated with urinary copper excretion (standardized ß = 0.39, p < 0.001), and urinary copper excretion was positively associated with u-LFABP (standardized ß = 0.29, p < 0.001). During a median follow-up of 8 years, 109 (16%) KTR developed graft failure. KTR with relatively high copper excretion were at higher risk of long-term graft failure (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.32-1.86 per log2, p < 0.001), independent of multiple potential confounders like eGFR, urinary protein excretion, and time after transplantation. A dose-response relationship was observed over increasing tertiles of copper excretion (HR: 5.03, 95% CI: 2.75-9.19, tertile 3 vs. 1, p < 0.001). u-LFABP was a significant mediator of this association (74% of indirect effect, p < 0.001). CONCLUSION: In KTR, urinary protein excretion is positively correlated with urinary copper excretion. In turn, higher urinary copper excretion is associated with an independent increased risk of kidney graft failure, with a substantial mediating effect through oxidative tubular damage. Further studies are warranted to investigate whether copper excretion-targeted interventions could improve kidney graft survival.


Asunto(s)
Trasplante de Riñón , Masculino , Humanos , Femenino , Trasplante de Riñón/efectos adversos , Cobre , Estudios Prospectivos , Riñón , Proteinuria/etiología , Receptores de Trasplantes , Factores de Riesgo , Supervivencia de Injerto
6.
Nephrol Dial Transplant ; 38(8): 1867-1879, 2023 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-36564033

RESUMEN

BACKGROUND: Long-term high-dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies have revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival. METHODS: Urinary lithium concentration was measured using inductively coupled plasma mass spectrometry in 642 stable kidney transplant recipients (KTRs). Graft failure was defined as the start of dialysis or retransplantation and kidney function decline was defined as a doubling of serum creatinine. RESULTS: The median urinary lithium excretion was 3.03 µmol/24 h [interquartile range (IQR) 2.31-4.01]. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 years (IQR 4.5-6.0), 79 (12%) KTRs developed graft failure and 127 (20%) KTRs developed kidney function decline. Higher urinary lithium excretion was associated with a lower risk of graft failure {hazard ratio [HR] per doubling 0.54 [95% confidence interval (CI) 0.38-0.79]} and kidney function decline [HR per doubling 0.73 (95% CI 0.54-0.99)]. These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was a significant effect modification with the use of proliferation inhibitors (P = .05) and baseline estimated glomerular filtration rate (eGFR; P < .001), with higher urinary lithium excretion being more protective in KTRs not using proliferation inhibitors and in KTRs with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with a reduced risk of all-cause mortality [HR 0.64 (95% CI 0.49-0.83); P = .001]. CONCLUSION: Dietary lithium intake may be a potentially modifiable, yet rather overlooked, risk factor for adverse long-term kidney graft outcomes and patient survival. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02811835.


Asunto(s)
Trasplante de Riñón , Trasplante de Riñón/efectos adversos , Litio/uso terapéutico , Diálisis Renal , Riñón , Factores de Riesgo , Receptores de Trasplantes
7.
Nephrol Dial Transplant ; 38(10): 2321-2329, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-36893803

RESUMEN

BACKGROUND: Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. METHODS: In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) µg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized ß 0.49, P < .001). CONCLUSIONS: Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.


Asunto(s)
Trasplante de Riñón , Selenio , Masculino , Humanos , Femenino , Trasplante de Riñón/efectos adversos , Estudios de Cohortes , Proteínas en la Dieta , Dieta , Receptores de Trasplantes , Factores de Riesgo
8.
Crit Rev Food Sci Nutr ; 63(15): 2426-2446, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34648415

RESUMEN

The slowdown, inhibition, or reversal of age-related decline (as a composite of disease, dysfunction, and, ultimately, death) by diet or natural compounds can be defined as dietary geroprotection. While there is no single reliable biomarker to judge the effects of dietary geroprotection, biomarker signatures based on omics (epigenetics, gene expression, microbiome composition) are promising candidates. Recently, omic biomarkers started to supplement established clinical ones such as lipid profiles and inflammatory cytokines. In this review, we focus on human data. We first summarize the current take on genetic biomarkers based on epidemiological studies. However, most of the remaining biomarkers that we describe, whether omics-based or clinical, are related to intervention studies. Then, because of their promising potential in the context of dietary geroprotection, we focus on the effects of berry-based interventions, which up to now have been mostly described employing clinical markers. We provide an aggregation and tabulation of all the recent systematic reviews and meta-analyses that we could find related to this topic. Finally, we present evidence for the importance of the "nutribiography," that is, the influence that an individual's history of diet and natural compound consumption can have on the effects of dietary geroprotection.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1975638.


Asunto(s)
Sistema Cardiovascular , Dieta , Humanos , Biomarcadores , Frutas
9.
Cell Mol Life Sci ; 79(9): 499, 2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36018414

RESUMEN

Human apolipoprotein E (APOE), originally known for its role in lipid metabolism, is polymorphic with three major allele forms, namely, APOEε2, APOEε3, and APOEε4, leading to three different human APOE isoforms. The ε4 allele is a genetic risk factor for Alzheimer's disease (AD); therefore, the vast majority of APOE research focuses on its role in AD pathology. However, there is increasing evidence for other functions of APOE through the involvement in other biological processes such as transcriptional regulation, mitochondrial metabolism, immune response, and responsiveness to dietary factors. Therefore, the aim of this review is to provide an overview of the potential novel functions of APOE and their characterization. The detection of APOE in various cell organelles points to previously unrecognized roles in mitochondria and others, although it is actually considered a secretory protein. Furthermore, numerous interactions of APOE with other proteins have been detected, providing indications for new metabolic pathways involving APOE. The present review summarizes the current evidence on APOE beyond its original role in lipid metabolism, to change the perspective and encourage novel approaches to future research on APOE and its isoform-dependent role in the cellular metabolism.


Asunto(s)
Enfermedad de Alzheimer , Fenómenos Biológicos , Apolipoproteínas E , Humanos , Mitocondrias , Isoformas de Proteínas
10.
Eur J Epidemiol ; 37(10): 1087-1105, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36245062

RESUMEN

The Food Chain Plus (FoCus) cohort was launched in 2011 for population-based research related to metabolic inflammation. To characterize this novel pathology in a comprehensive manner, data collection included multiple omics layers such as phenomics, microbiomics, metabolomics, genomics, and metagenomics as well as nutrition profiling, taste perception phenotyping and social network analysis. The cohort was set-up to represent a Northern German population of the Kiel region. Two-step recruitment included the randomised enrolment of participants via residents' registration offices and via the Obesity Outpatient Centre of the University Medical Center Schleswig-Holstein (UKSH). Hence, both a population- and metabolic inflammation- based cohort was created. In total, 1795 individuals were analysed at baseline. Baseline data collection took place between 2011 and 2014, including 63% females and 37% males with an age range of 18-83 years. The median age of all participants was 52.0 years [IQR: 42.5; 63.0 years] and the median baseline BMI in the study population was 27.7 kg/m2 [IQR: 23.7; 35.9 kg/m2]. In the baseline cohort, 14.1% of participants had type 2 diabetes mellitus, which was more prevalent in the subjects of the metabolic inflammation group (MIG; 31.8%). Follow-up for the assessment of disease progression, as well as the onset of new diseases with changes in subject's phenotype, diet or lifestyle factors is planned every 5 years. The first follow-up period was finished in 2020 and included 820 subjects.


Asunto(s)
Diabetes Mellitus Tipo 2 , Femenino , Humanos , Masculino , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Cadena Alimentaria , Inflamación , Obesidad/epidemiología , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años
11.
Eur J Nutr ; 61(3): 1363-1375, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34825958

RESUMEN

PURPOSE: Experimental evidence suggests positive effects of boron on health and metabolism, but human data are still scarce. We aimed to identify dietary and cardio-metabolic correlates of plasma boron concentrations in the general population. METHODS: In a community-based sample (n = 899, 57% men, mean age 61 years), plasma boron (median [IQR]: 33.80 µg/L [25.61; 44.65]) concentrations were measured by inductively coupled plasma-mass spectrometry. Overall (PDI), healthy (hPDI), and unhealthy (uPDI) plant-based diet indices were derived from a validated food frequency questionnaire. Reduced rank regression (RRR) yielded a dietary pattern explaining 30% of the variation of circulating boron. Cross-sectional associations of dietary indices and cardio-metabolic traits with plasma boron concentrations were assessed using multivariable-adjusted linear regression analysis. RESULTS: The RRR pattern was characterized by high intake of fruits, nuts/seeds, tea, wine and low intake of e.g. bread, poultry, processed meat, chocolate/sweets, and soft drinks. 10-point increments in PDI, hPDI, and uPDI were associated with 8.7% (95% CI: 4.2; 13.4), 10.4% (95% CI: 6.6; 14.3), and -8.8% (95% CI: -12.1; -5.4) change in plasma boron concentrations, respectively. Age and phosphate were directly, while BMI, plasma lipid concentrations, and CRP were inversely associated with circulating boron. Plasma boron concentrations were higher in summer vs. winter, in individuals taking vs. not taking antihypertensive medication, and in individuals with high or medium vs. low education level. CONCLUSION: Higher plasma boron concentrations appeared to associate with a healthier diet, were related to lower BMI and a more favorable cardio-metabolic risk profile, and showed seasonal variations.


Asunto(s)
Boro , Dieta , Estudios Transversales , Dieta Saludable , Femenino , Frutas , Humanos , Masculino , Persona de Mediana Edad
12.
Eur J Nutr ; 61(2): 973-984, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34677681

RESUMEN

PURPOSE: In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR. METHODS: We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires. RESULTS: Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank < 0.001). Cox regression analyses showed that high boron excretion was strongly associated with lower risk of mortality, independent of age, sex, estimated glomerular filtration rate and history of cardiovascular disease (HR per doubling: 0.51, 95% CI: 0.40 to 0.66, P < 0.001). CONCLUSION: Boron may be an overlooked target to improve long-term survival among KTR and potentially other patients, likely through pathways other than inflammation or the methionine-homocysteine cycle that were previously suggested. Interventional trials are warranted to confirm the potential of dietary boron supplementation in KTR and other patient populations.


Asunto(s)
Boro , Trasplante de Riñón , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Receptores de Trasplantes
13.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34769143

RESUMEN

The fruit fly Drosophila melanogaster has become a valuable model organism in nutritional science, which can be applied to elucidate the physiology and the biological function of nutrients, including trace elements. Importantly, the application of chemically defined diets enables the supply of trace elements for nutritional studies under highly standardized dietary conditions. Thus, the bioavailability and bioactivity of trace elements can be systematically monitored in D. melanogaster. Numerous studies have already revealed that central aspects of trace element homeostasis are evolutionary conserved among the fruit fly and mammalian species. While there is sufficient evidence of vital functions of boron (B) in plants, there is also evidence regarding its bioactivity in animals and humans. Lithium (Li) is well known for its role in the therapy of bipolar disorder. Furthermore, recent findings suggest beneficial effects of Li regarding neuroprotection as well as healthy ageing and longevity in D. melanogaster. However, no specific essential function in the animal kingdom has been found for either of the two elements so far. Here, we summarize the current knowledge of Li and B bioactivity in D. melanogaster in the context of health and disease prevention.


Asunto(s)
Boro/metabolismo , Drosophila melanogaster , Litio/metabolismo , Modelos Animales , Oligoelementos/metabolismo , Animales
14.
J Clin Biochem Nutr ; 66(1): 24-35, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32001953

RESUMEN

To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity.

15.
Int J Mol Sci ; 20(9)2019 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-31085998

RESUMEN

In this study, we provide experimental evidence that a maternally inherited polymorphism in the mitochondrial cytochrome b gene (mt-Cytb; m.15124A>G, Ile-Val) in mitochondrial complex III resulted in middle-aged obesity and higher susceptibility to diet-induced obesity, as well as age-related inflammatory disease, e.g., ulcerative dermatitis, in mice. As a consequence of the gene variation, we observed alterations in body composition, metabolism and mitochondrial functions, i.e., increased mitochondrial oxygen consumption rate and higher levels of reactive oxygen species, as well as in the commensal bacterial composition in the gut, with higher abundance of Proteobacteria in mice carrying the variant. These observations are in line with the previously described links of the mitochondrial complex III gene with obesity and metabolic diseases in humans. Given that these functional changes by the G variant at m.15124 in the mt-Cytb are already present in young mice that were kept under normal condition, it is plausible that the m.15124A>G variant is a disease susceptibility modifier to the diseases induced by additional stressors, i.e., dietary and/or aging stress, and that the variant results in the higher incidence of clinical diseases presentation in C57BL/6J-mt129S1/SvlmJ than C57BL/6J mice. Thus, mtDNA variants could be potential biomarkers to evaluate the healthspan.


Asunto(s)
ADN Mitocondrial/genética , Genes Mitocondriales/genética , Animales , Bacteroidetes/genética , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Membranas Mitocondriales/metabolismo , Mutación/genética , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Polimorfismo de Nucleótido Simple/genética , Especies Reactivas de Oxígeno/metabolismo
16.
Mar Drugs ; 16(10)2018 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-30309000

RESUMEN

To sustainably produce marine fish with a high lipid quality rich in omega-3 fatty acids, alternative sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are being identified. Moreover, the use of bioactive compounds that would stimulate the in vivo fatty acid synthesis, such as resveratrol (RV), would reduce the dependence on fish oil in aquafeeds. Gilthead sea bream (Sparus aurata) were fed four experimental diets combining two fish oil levels (6% dry matter (DM); 2% DM) with or without 0.15% DM resveratrol supplementation (F6, F2, F6 + RV, F2 + RV) for two months. Additionally, the fish were challenged either at 19 °C or 23 °C. A higher water temperature promoted their feed intake and growth, resulting in an increased crude lipid content irrespective of dietary treatment. The fatty acid composition of different tissues was significantly affected by the holding temperature and dietary fish oil level. The dietary RV significantly affected the hepatic EPA and DHA content of fish held at 19 °C. The observed effect of RV may be partly explained by alterations of the mRNA steady-state levels of ∆6-desaturase and ß-oxidation-related genes. Besides the relevant results concerning RV-mediated regulation of fatty acid synthesis in marine fish, further studies need to be conducted to clarify the potential value of RV to enhance fillet lipid quality.


Asunto(s)
Ácidos Grasos/genética , Ácidos Grasos/metabolismo , Aceites de Pescado/farmacología , Expresión Génica/efectos de los fármacos , Resveratrol/farmacología , Dorada/metabolismo , Alimentación Animal , Animales , Dieta/métodos , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos Omega-3/metabolismo , Expresión Génica/genética , Dorada/genética , Temperatura
17.
Int J Mol Sci ; 19(1)2018 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-29324667

RESUMEN

In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase, NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2) and longevity-related genes, including sirtuin 2, spargel, and I'm Not Dead Yet. Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w1118 D. melanogaster.


Asunto(s)
Antioxidantes/farmacología , Composición Corporal , Proteínas de Drosophila/genética , Drosophila melanogaster/efectos de los fármacos , Longevidad , Estrés Oxidativo , Estilbenos/farmacología , Animales , Antioxidantes/administración & dosificación , Suplementos Dietéticos , Proteínas de Drosophila/metabolismo , Femenino , Locomoción , Masculino , Resveratrol , Estilbenos/administración & dosificación
18.
Clin Sci (Lond) ; 131(20): 2549-2560, 2017 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-28935809

RESUMEN

Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein, and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared with the control group, mice fed the chocolate liquor had larger plaque areas in the descending aorta and aortic root, which were attributed to a higher mass of vascular smooth muscle cells (VSMCs) and collagen. Vascular lipid deposits and calcification areas did not differ between the two groups. The aortic tissue level of interleukin-6 (IL-6) mRNA was 5-fold higher in the mice fed chocolate liquor than in the control mice. Chocolate-fed mice exhibited an increased hepatic saturated to polyunsaturated fatty acid ratio than the controls. Although the chocolate liquor contained 14 µg/kg of vitamin D2, the chocolate liquor-fed mice did not have measurable 25-hydroxyvitamin D2 in the serum. These mice even showed a 25% reduction in the level of 25-hydroxyvitamin D3 compared with the control mice. Overall, present data may contribute to our understanding how chocolate constituents can impact vascular lesion development.


Asunto(s)
Aterosclerosis/terapia , Chocolate , Dieta Alta en Grasa , Placa Aterosclerótica/patología , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/metabolismo , Aterosclerosis/genética , Ergocalciferoles/administración & dosificación , Ergocalciferoles/farmacología , Masculino , Ratones Noqueados
19.
FASEB J ; 30(2): 948-58, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26538555

RESUMEN

Dietary isoflavones, a group of secondary plant compounds that exhibit phytoestrogenic properties, are primarily found in soy. Prunetin, a representative isoflavone, was recently found to affect cell signaling in cultured cells; however, in vivo effects remain elusive. In this study, the model organism Drosophila melanogaster was used to investigate the effects of prunetin in vivo with respect to lifespan, locomotion, body composition, metabolism, and gut health. Adult flies were chronically administered a prunetin-supplemented diet. Prunetin improved median survival by 3 d, and climbing activity increased by 54% in males. In comparison with the females, male flies exhibited lower climbing activity, which was reversed by prunetin intake. Furthermore, prunetin-fed males exhibited increased expression of the longevity gene Sirtuin 1 (Sir2) (22%), as well as elevated AMPK activation (51%) and triglyceride levels (29%), whereas glucose levels decreased (36%). As females are long-lived compared with their male counterparts and exhibit higher triglyceride levels, prunetin apparently "feminizes" male flies via its estrogenicity. We conclude that the lifespan-prolonging effects of prunetin in the male fruit fly depend on changes in AMPK-regulated energy homeostasis via male "feminization." Collectively, we identified prunetin as a plant bioactive compound capable of improving health status and survival in male D. melanogaster.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Isoflavonas/farmacología , Locomoción/efectos de los fármacos , Fitoestrógenos/farmacología , Caracteres Sexuales , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Activación Enzimática/efectos de los fármacos , Femenino , Glucosa/metabolismo , Histona Desacetilasas/metabolismo , Masculino , Sirtuinas/metabolismo , Triglicéridos/metabolismo
20.
Mar Drugs ; 15(8)2017 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-28800114

RESUMEN

To produce fish of a high quality that are rich in omega-3 fatty acids (n-3 FA) and simultaneously generate more sustainable aquaculture, the combined use of phytochemicals and vegetable oils in fish feed seems to be a promising approach. Resveratrol (RV) potentially induces endogenous fatty acid synthesis, resulting in elevated n-3 FA levels in fish. RV putatively influences ∆6-desaturase, the key enzyme in FA metabolism, and serves as a ligand for PPARα, a transcription factor regulating ß-oxidation. Rainbow trout (36.35 ± 0.03 g) were randomly allocated into six groups and fed diets with reduced fish oil levels (F4 = 4%, F2 = 2% and F0 = 0% of dry matter) supplemented with 0.3% (w/w) RV (F4 + RV, F2 + RV and F0 + RV). RV significantly affected FA composition in liver tissue and whole fish homogenates. 20:5n-3 (EPA) and 22:6n-3 (DHA) were significantly increased whereas precursor FA were diminished in fish fed the F2 + RV and F0 + RV diets when compared to F4 + RV and F0. RV significantly elevated ∆6-desaturase protein levels in the livers of F0 + RV fed animals. Hepatic mRNA expression of ∆6-desaturase, PPARα, and its target genes were affected by the dietary fish oil level and not by dietary RV. The results of this study indicated a potential benefit of supplementing RV in fish oil deprived diets elevating n-3 FA levels in rainbow trout.


Asunto(s)
Ácidos Grasos/metabolismo , Oncorhynchus mykiss , Estilbenos/metabolismo , Alimentación Animal , Animales , Acuicultura , Dieta , Grasas Insaturadas en la Dieta/metabolismo , Suplementos Dietéticos/análisis , Ácidos Grasos/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-3/metabolismo , Aceites de Pescado/química , Hígado/metabolismo , Aceites de Plantas/química , Resveratrol
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