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The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.
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Ácidos Docosahexaenoicos , Ácidos Grasos Insaturados , Feto , Hígado , Fosfolípidos , Animales , Femenino , Embarazo , Hígado/metabolismo , Fosfolípidos/metabolismo , Ácidos Grasos Insaturados/metabolismo , Ratones , Ácidos Docosahexaenoicos/metabolismo , Feto/metabolismo , Receptores X del Hígado/metabolismo , Receptores X del Hígado/genética , Metabolismo de los Lípidos/genética , Ratones Endogámicos C57BL , Transducción de Señal , Masculino , Lipidómica , Ratones NoqueadosRESUMEN
BACKGROUND: Bees provide essential pollination services for many food crops and are critical in supporting wild plant diversity. However, the dietary landscape of pollen food sources for social and solitary bees has changed because of agricultural intensification and habitat loss. For this reason, understanding the basic nutrient metabolism and meeting the nutritional needs of bees is becoming an urgent requirement for agriculture and conservation. We know that pollen is the principal source of dietary fat and sterols for pollinators, but a precise understanding of what the essential nutrients are and how much is needed is not yet clear. Sterols are key for producing the hormones that control development and may be present in cell membranes, where fatty-acid-containing species are important structural and signalling molecules (phospholipids) or to supply, store and distribute energy (glycerides). AIM OF THE REVIEW: In this critical review, we examine the current general understanding of sterol and lipid metabolism of social and solitary bees from a variety of literature sources and discuss implications for bee health. KEY SCIENTIFIC CONCEPTS OF REVIEW: We found that while eusocial bees are resilient to some dietary variation in sterol supply the scope for this is limited. The evidence of both de novo lipogenesis and a dietary need for particular fatty acids (FAs) shows that FA metabolism in insects is analogous to mammals but with distinct features. Bees rely on their dietary intake for essential sterols and lipids in a way that is dependent upon pollen availability.
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Fitosteroles , Esteroles , Abejas , Animales , Metabolismo de los Lípidos , Metabolómica , Productos Agrícolas , Ácidos Grasos , MamíferosRESUMEN
AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Gestacional , Hiperglucemia , Hiperinsulinismo , Hipoglucemia , Preeclampsia , Femenino , Humanos , Recién Nacido , Embarazo , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/complicaciones , Hiperglucemia/complicacionesRESUMEN
Sterols have several roles in planta, including as membrane components. Sterols are also essential nutrients for insects. Based on this, and the different functions of leaves and pollen, we tested the hypotheses that (a) the sterolome is different in leaves and pollen from the same plant, (b) pollens from wind- and insect pollinated plants comprise different sterols, and (c) sterol provision in pollen-rewarding angiosperms differs from nectar-rewarding species. A novel approach to sterolomics was developed, using LCMS to determine the sterol profile of leaf and pollen from a taxonomically diverse range of 36 plant species. Twenty-one sterols were identified unambiguously, with several more identified in trace amounts. C29 sterols dominated the sterolome in most plants. The sterol composition was significantly different in leaf and pollen and their main sterols evolved in different ways. The sterolome of pollen from animal- and wind-pollinated was also significantly different, but not between nectar- and pollen-rewarding species. Our results suggest that the sterol composition in different plant tissues is linked to their biological functions. Sterol composition in pollen might be driven by physical role rather than the nutrient needs of pollinating insects.
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Fitosteroles , Polinización , Animales , Néctar de las Plantas , Esteroles , Hojas de la Planta , Polen , Insectos , FloresRESUMEN
AIMS: Precision medicine has revolutionized our understanding of type 1 diabetes and neonatal diabetes but has yet to improve insight into gestational diabetes mellitus (GDM), the most common obstetric complication and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1 hour, 2 hours) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles. METHODS: 867 pregnant women with obesity (body mass index ≥ 30 kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks' gestation (75 g oral glucose tolerance test OGTT; World Health Organization criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analyzed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterized by homeostatic model assessment 2b and 2s, respectively. RESULTS: In women who developed GDM (n = 241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycemia had comparable insulin secretion and sensitivity to euglycemic women, potentially indicative of a novel mechanistic pathway. CONCLUSIONS: Patterns of glycemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycemia reflects a different mechanistic pathway for targeted management.
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Diabetes Gestacional , Hiperglucemia , Resistencia a la Insulina , Recién Nacido , Femenino , Embarazo , Humanos , Mujeres Embarazadas , Glucemia/análisis , Medicina de Precisión , Insulina/metabolismo , Obesidad/complicaciones , LípidosRESUMEN
There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein-high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring's hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.
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Encéfalo , Semen , Femenino , Ratones , Masculino , Animales , Ratones Endogámicos C57BL , Homeostasis , LípidosRESUMEN
Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+ dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+ pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function. We demonstrate that stimulating the TRP-NAD+ pathway with NAD+ precursors improves hepatic mitochondrial and overall metabolic function through SIRT1 modulation. Activating SIRT1 is sufficient to induce improvement in metabolic functions. Our findings indicate that modulating the TRP-NAD+ pathway can improve liver metabolic function in a mouse model of severe malnutrition. These results could lead to the development of new interventions for children with severe malnutrition.
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Hepatopatías , NAD , Ratones , Animales , TriptófanoRESUMEN
Male fertility, as manifest by the quantity and progressive motility of spermatozoa, is negatively impacted by obesity, dyslipidaemia and metabolic disease. However, the relative distribution of lipids in spermatozoa and the two compartments which supply lipids for spermatogenesis (seminal fluid and blood serum) has not been studied. We hypothesised that altered availability of lipids in blood serum and seminal fluid may affect the lipid composition and progressive motility of sperm. 60 men of age 35 years (median (range 20-45) and BMI 30.4 kg/m2 (24-36.5) under preliminary investigation for subfertility were recruited at an NHS clinic. Men provided samples of serum and semen, subject to strict acceptance criteria, for analysis of spermatozoa count and motility. Blood serum (n = 60), spermatozoa (n = 26) and seminal fluid (n = 60) were frozen for batch lipidomics analysis. Spermatozoa and seminal fluid had comparable lipid composition but showed marked differences with the serum lipidome. Spermatozoa demonstrated high abundance of ceramides, very-long-chain fatty acids (C20-22), and certain phospholipids (sphingomyelins, plasmalogens, phosphatidylethanolamines) with low abundance of phosphatidylcholines, cholesterol and triglycerides. Men with spermatozoa of low progressive motility had evidence of fewer concentration gradients for many lipid species between blood serum and spermatozoa compartments. Spermatozoa are abundant in multiple lipid species which are likely to contribute to key cellular functions. Lipid metabolism shows reduced regulation between compartments in men with spermatozoa with reduced progressive motility.
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Semen , Motilidad Espermática , Adulto , Ceramidas/metabolismo , Colesterol/metabolismo , Ácidos Grasos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Plasmalógenos , Semen/metabolismo , Recuento de Espermatozoides , Motilidad Espermática/fisiología , Espermatozoides/metabolismo , Esfingomielinas/metabolismo , Triglicéridos/metabolismo , Adulto JovenRESUMEN
This protocol outlines a translational lipidomic approach to discover lipid biomarkers that could predict morphometric body and histological organ measurements (e.g., weight and adiposity gains) during specific stages of life (e.g., early life). We describe procedures ranging from animal experimentation and histological analyses to downstream analytical steps through lipid profiling, both in mice and humans. This protocol represents a reliable and versatile approach to translate and validate candidate lipid biomarkers from animal models to a human cohort. For complete details on the use and execution of this protocol, please refer to Olga et al. (2021).
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Lipidómica , Lípidos , Lactante , Humanos , Animales , Ratones , Modelos Animales de EnfermedadRESUMEN
The underlying mechanisms driving paternally-programmed metabolic disease in offspring remain poorly defined. We fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using artificial insemination, in combination with vasectomised male mating, we generated offspring using either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Offspring from either LPD sperm or seminal fluid display elevated body weight and tissue dyslipidaemia from just 3 weeks of age. These changes become more pronounced in adulthood, occurring in conjunction with altered hepatic metabolic and inflammatory pathway gene expression. Second generation offspring also display differential tissue lipid abundance, with profiles similar to those of first generation adults. These findings demonstrate that offspring metabolic homeostasis is perturbed in response to a suboptimal paternal diet with the effects still evident within a second generation.
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Dieta con Restricción de Proteínas , Semen , Animales , Padre , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Much evidence for diabetes mellitus being associated with dysregulated lipid metabolism has been accrued from studies using blood plasma. However, the systemic dysregulation these results point to is not understood. This study used Lipid Traffic Analysis on data from a mouse model of diabetes to test the hypothesis that the systemic control of lipid metabolism differed in a model of diabetes. This provided eidence for changes in the systemic control of both triglyceride and phospholipid metabolism that were not attributable to dietary intake. This supports the conclusion that diabetes is a systemic condition associated with dysregulated lipid metabolism through several pathways.
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Diabetes Mellitus , Metabolismo de los Lípidos , Animales , Modelos Animales de Enfermedad , Metabolómica , Ratones , Triglicéridos/metabolismoRESUMEN
Genome-wide association studies in adults have identified variants in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6-0.9) and a lower grade of portal inflammation (p < 0.001). rs2642438G>A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective -TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down-regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.
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17-Hidroxiesteroide Deshidrogenasas , Proteínas Mitocondriales , Enfermedad del Hígado Graso no Alcohólico , Oxidorreductasas , 17-Hidroxiesteroide Deshidrogenasas/genética , Niño , Estudio de Asociación del Genoma Completo , Humanos , Hidroxiesteroides , Proteínas Mitocondriales/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Oxidorreductasas/genética , OximasRESUMEN
CONTEXT: Gestational diabetes (GDM) affects 20 million women/year worldwide and is associated with childhood obesity. Infants of affected mothers have increased adiposity from birth, which leads to obesity in later life. However, it remains unknown whether the effect of GDM upon neonatal body composition is due to hyperglycemia alone or is mediated by other pathways. OBJECTIVE: To investigate plasma lipid profiles in obese women according to GDM diagnosis, infant birthweight percentiles, and adiposity. DESIGN: Prospective cohort from UPBEAT trial (ISRCTN 89971375). SETTING: Hospital and community. PATIENTS: 867 obese pregnant women recruited in early pregnancy, assessed at 28 weeks for GDM. Offspring anthropometry was assessed at birth. OUTCOME (PRESPECIFIED): Neonatal birth percentile and abdominal circumference. METHODS: Lipidomic profiling in the fasting plasma oral glucose tolerance test sample using direct infusion mass spectrometry. Analysis included logistic/linear regression, unadjusted and adjusted for maternal age, body mass index, parity, ethnicity, UPBEAT trial arm, and fetal sex. The limit of significance was Pâ =â 0.05 for offspring anthropometry and Pâ =â 0.002 for lipidomic data. RESULTS: GDM in obese women was associated with elevated plasma concentrations of specific diglycerides [DG(32:0)] and triglycerides [TG(48:0), (50:1), (50:2)] containing fatty acids (16:0), (16:1), (18:0), and (18:1), consistent with increased de novo lipogenesis. In the whole cohort, these species were associated with birthweight percentile and neonatal abdominal circumference. Effects upon infant abdominal circumference remained significant after adjustment for maternal glycemia. CONCLUSIONS: Increased de novo lipogenesis-related species in pregnant women with obesity and GDM are associated with measures of offspring adiposity and may be a target for improving lifelong health.
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Diabetes Gestacional , Obesidad Infantil , Adiposidad , Peso al Nacer , Índice de Masa Corporal , Niño , Femenino , Humanos , Lactante , Recién Nacido , Metabolismo de los Lípidos , Obesidad Infantil/complicaciones , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.
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Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Adulto , Enfermedades Cardiovasculares/etiología , Niño , Estudios Transversales , Humanos , Lipidómica , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , TriglicéridosRESUMEN
BACKGROUND: Gestational diabetes is associated with increased risk of type 2 diabetes mellitus and cardiovascular disease for the mother in the decade after delivery. However, the molecular mechanisms that drive these effects are unknown. Recent studies in humans have shown that lipid metabolism is dysregulated before diagnosis of and during gestational diabetes and we have shown previously that lipid metabolism is also altered in obese female mice before, during and after pregnancy. These observations led us to the hypothesis that this persistent dysregulation reflects an altered control of lipid distribution throughout the organism. METHODS: We tested this in post-weaning (PW) dams using our established mouse model of obese GDM (high fat, high sugar, obesogenic diet) and an updated purpose-built computational tool for plotting the distribution of lipid variables throughout the maternal system (Lipid Traffic Analysis v2.3). RESULTS: This network analysis showed that unlike hyperglycaemia, lipid distribution and traffic do not return to normal after pregnancy in obese mouse dams. A greater range of phosphatidylcholines was found throughout the lean compared to obese post-weaning dams. A range of triglycerides that were found in the hearts of lean post-weaning dams were only found in the livers of obese post-weaning dams and the abundance of odd-chain FA-containing lipids differed locally in the two groups. We have therefore shown that the control of lipid distribution changed for several metabolic pathways, with evidence for changes to the regulation of phospholipid biosynthesis and FA distribution, in a number of tissues. CONCLUSIONS: We conclude that the control of lipid metabolism is altered following an obese pregnancy. These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Gestacional/metabolismo , Dieta Alta en Grasa/efectos adversos , Femenino , Metabolismo de los Lípidos , Ratones , Embarazo , DesteteRESUMEN
OBJECTIVE: Polyunsaturated fatty acid (PUFA) supplements have been trialled as a treatment for a number of conditions and produced a variety of results. This variety is ascribed to the supplements, that often comprise a mixture of fatty acids, and to different effects in different organs. In this study, we tested the hypothesis that the supplementation of individual PUFAs has system-level effects that are dependent on the molecular structure of the PUFA. METHODS: We undertook a network analysis using Lipid Traffic Analysis to identify both local and system-level changes in lipid metabolism using publicly available lipidomics data from a mouse model of supplementation with FA(20:4n-6), FA(20:5n-3), and FA(22:6n-3); arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, respectively. Lipid Traffic Analysis is a new computational/bioinformatics tool that uses the spatial distribution of lipids to pinpoint changes or differences in control of metabolism, thereby suggesting mechanistic reasons for differences in observed lipid metabolism. RESULTS: There was strong evidence for changes to lipid metabolism driven by and dependent on the structure of the supplemented PUFA. Phosphatidylcholine and triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositol showed considerable change in both which variables and the number of them, in a highly PUFA-dependent manner. There was also evidence for changes to the endogenous biosynthesis of fatty acids and to both the elongation and desaturation of fatty acids. CONCLUSIONS: These results show that the full biological impact of PUFA supplementation is far wider than any single-organ effect and implies that supplementation and dosing with PUFAs require a system-level assessment.
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Ácidos Grasos Insaturados , Metabolismo de los Lípidos , Animales , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos , Ácidos Grasos Insaturados/metabolismo , RatonesRESUMEN
BACKGROUND: The paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming. However, we do not know how this is propagated to the offspring. OBJECTIVES: We tested the hypothesis that the changes in lipid metabolism that are driven by paternal diet are propagated through spermatozoa and not seminal plasma. METHODS: We applied an updated, purpose-built computational network analysis tool to characterise control of lipid metabolism systemically (Lipid Traffic Analysis v2.3) on a known mouse model of paternal nutritional programming. RESULTS: The analysis showed that the two possible routes for programming effects, the sperm (genes) and seminal plasma (influence on the uterine environment), both have a distinct effect on the offspring's lipid metabolism. Further, the programming effects in offspring suggest that changes in lipid distribution are more important than alterations in lipid biosynthesis. CONCLUSIONS: These results show how the uterine environment and genes both affect lipid metabolism in offspring, enhancing our understanding of the link between parental diet and metabolism in offspring.
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Metabolismo de los Lípidos , Semen , Animales , Padre , Humanos , Masculino , Metabolómica , Ratones , Espermatozoides/metabolismoRESUMEN
Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.
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Feto/metabolismo , Metabolismo de los Lípidos/fisiología , Miocardio/metabolismo , Obesidad Materna/fisiopatología , Animales , Femenino , Lipidómica , Masculino , Ratones , Miocardio/química , Embarazo , Transcriptoma/fisiologíaRESUMEN
The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams' systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.
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Diabetes Gestacional/patología , Metabolismo de los Lípidos , Lipidómica/métodos , Lípidos/análisis , Obesidad/fisiopatología , Animales , Glucemia/análisis , Diabetes Gestacional/etiología , Diabetes Gestacional/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Ratones , EmbarazoRESUMEN
Detailed molecular analysis is of increasing importance in research into the regulation of biochemical pathways, organismal growth and disease. Lipidomics in particular is increasingly sought after as it provides insight into molecular species involved in energy storage, signalling and fundamental cellular structures. This has led to the use of a range of tools and techniques to acquire lipidomics data. 31P NMR for lipidomics offers well-resolved head group/lipid class analysis, structural data that can be used to inform and strengthen interpretation of mass spectrometry data and part of a priori structural determination. In the present study, we codify the use of 31P NMR for lipidomics studies to make the technique more accessible to new users and more useful for a wider range of questions. The technique can be used in isolation (phospholipidomics) or as a part of determining lipid composition (lipidomics). We describe the process from sample extraction to data processing and analysis. This pipeline is important because it allows greater thoroughness in lipidomics studies and increases scope for answering scientific questions about lipid-containing systems.