Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily ...accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard operating procedures must be followed. Inappropriate sample collection or storage can indeed result in high variability, interferences with instrumentation or degradation of metabolites. In this review, we will first highlight important general factors that should be considered when planning sample collection in the study design of metabolomic studies, such as nutritional status and circadian rhythm. Then, we will discuss in more detail the specific procedures that have been described for optimal pre-analytical handling of the most commonly used matrices (urine, blood, feces, tissues and cells).
Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. ...Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/-) fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We recently demonstrated that chronic dietary exposure to a mixture of pesticides at low-doses induced sexually dimorphic obesogenic and diabetogenic effects in adult mice. Perinatal pesticide ...exposure may also be a factor in metabolic disease etiology. However, the long-term consequences of perinatal pesticide exposure remain controversial and largely unexplored.
Here we assessed how perinatal exposure to the same low-dose pesticide cocktail impacted metabolic homeostasis in adult mice.
Six pesticides (boscalid, captan, chlopyrifos, thiachloprid, thiophanate, and ziram) were incorporated in food pellets. During the gestation and lactation periods, female (F0) mice were fed either a pesticide-free or a pesticide-enriched diet at doses exposing them to the tolerable daily intake (TDI) level for each compound, using a 1:1 body weight scaling from humans to mice. All male and female offsprings (F1) were then fed the pesticide-free diet until 18 weeks of age, followed by challenge with a pesticide-free high-fat diet (HFD) for 6 weeks. Metabolic parameters, including body weight, food and water consumption, glucose tolerance, and urinary and fecal metabolomes, were assessed over time. At the end of the experiment, we evaluated energetic metabolism and microbiota activity using biochemical assays, gene expression profiling, and 1H NMR-based metabolomics in the liver, urine, and feces.
Perinatal pesticide exposure did not affect body weight or energy homeostasis in 6- and 14-week-old mice. As expected, HFD increased body weight and induced metabolic disorders as compared to a low-fat diet. However, HFD-induced metabolic perturbations were similar between mice with and without perinatal pesticide exposure. Interestingly, perinatal pesticide exposure induced time-specific and sex-specific alterations in the urinary and fecal metabolomes of adult mice, suggesting long-lasting changes in gut microbiota.
Perinatal pesticide exposure induced sustained sexually dimorphic perturbations of the urinary and fecal metabolic fingerprints, but did not significantly influence the development of HFD-induced metabolic diseases.
ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in ...mammals. Here, we used ELOVL2-ablated (Elovl2−/−) mice to show that the PUFAs with 24–30 carbon atoms of the ω-6 family in testis are indispensable for normal sperm formation and fertility in male mice. The lack of Elovl2 was associated with a complete arrest of spermatogenesis, with seminiferous tubules displaying only spermatogonia and primary spermatocytes without further germinal cells. Furthermore, based on acyl-CoA profiling, heterozygous Elovl2+/− male mice exhibited haploinsufficiency, with reduced levels of C28:5 and C30:5n-6 PUFAs, which gave rise to impaired formation and function of haploid spermatides. These new insights reveal a novel mechanism involving ELOVL2-derived PUFAs in mammals and previously unrecognized roles for C28 and C30 n-6 PUFAs in male fertility. In accordance with the function suggested for ELOVL2, the Elovl2−/− mice show distorted levels of serum C20 and C22 PUFAs from both the n-3 and the n-6 series. However, dietary supplementation with C22:6n-3 could not restore male fertility to Elovl2+/− mice, suggesting that the changes in n-6 fatty acid composition seen in the testis of the Elovl2+/− mice, cannot be compensated by increased C22:6n-3 content.
The unusually high number of volcanoes in the Ecuadorian Arc, located in the deformation zone of the continental North Andean Sliver, coincides with the projection of the major oceanic structures ...observed in the Nazca Plate, such as the Carnegie Ridge and the Grijalva fracture zone. Although the relationship between this tectonic setting and volcanism has been widely discussed in the literature, their temporal relationship has not been thoroughly investigated due to the lack of geochronological data. We present here 20 new KAr and 2 40Ar/39Ar ages obtained for 7 volcanoes of the central segment of the Ecuadorian arc, which together with previous data show that volcanism in this area started at ∼1.3 Ma. A notable increase in volcanic activity occurred since ∼0.6 Ma, when the formation of a dozen volcanoes occurred in a relatively small area of the central segment. While this arrangement of volcanoes, here referred to as a “volcanic cluster”, appears to be controlled by crustal tectonic structures, the order of onset of these volcanoes and their eruptive activity does not show clear migration patterns over time. However, the presence of older volcanoes in the north of the central segment suggests a possible southward extension of volcanism between ∼1.3 and ∼ 0.6 Ma. Finally, based on the cumulative bulk volumes calculated for the volcanic edifices over time, we infer that the magmatic productivity rate has been roughly constant during the last ∼550 kyr in this area.
•Volcanic activity in the central Ecuadorian Andes occurred since at least ∼1.3 Ma•An increase in volcanic activity took place to the south since ∼0.6 Ma.•The predominance of older volcanoes to the north suggests an extension of volcanism.•Crustal tectonic structures had a key role in the spatial arrangement of volcanoes•The overall volcanic output rate has been roughly stable during the last ∼0.6 Ma.
We have reconstructed the eruptive chronology of the Ampato–Sabancaya volcanic complex (Southern Peru) on the basis of extensive fieldwork, and a large dataset of geochronological (40K–40Ar, 14C and ...3He) and geochemical (major and trace element) data. This volcanic complex is composed of two successive edifices that have experienced discontinuous volcanic activity from Middle Pleistocene to Holocene times. The Ampato compound volcano consists of a basal edifice constructed over at least two cone-building stages dated at 450–400ka and 230–200ka. After a period of quiescence, the Ampato Upper edifice was constructed firstly during an effusive stage (80–70ka), and then by the formation of three successive peaks: the Northern, Southern (40–20ka) and Central cones (20–10ka). The Southern peak, which is the biggest, experienced large explosive phases, resulting in deposits such as the Corinta plinian fallout. During the Holocene, eruptive activity migrated to the NE and constructed the mostly effusive Sabancaya edifice. This cone comprised many andesitic and dacitic blocky lava flows and a young terminal cone, mostly composed of pyroclastic material. Most samples from the Ampato–Sabancaya define a broad high-K magmatic trend composed of andesites and dacites with a mineral assemblage of plagioclase, amphibole, biotite, ortho- and clino-pyroxene, and Fe–Ti oxides. A secondary trend also exists, corresponding to rare dacitic explosive eruptions (i.e. Corinta fallout and flow deposits). Both magmatic trends are derived by fractional crystallisation involving an amphibole-rich cumulate with variable amounts of upper crustal assimilation.
A marked change in the overall eruptive rate has been identified between Ampato (~0.1km3/ka) and Sabancaya (0.6–1.7km3/ka). This abrupt change demonstrates that eruptive rates have not been homogeneous throughout the volcano's history. Based on tephrochronologic studies, the Late Holocene Sabancaya activity is characterised by strong vulcanian events, although its erupted volume remained low and only produced a local impact through ash fallout. We have identified at least 6 eruptions during the last 4–5ka, including the historical AD 1750–1784 and 1987–1998 events. On the basis of this recurrent low-to-moderate explosive activity, Sabancaya must be considered active and a potentially threatening volcano.
•Ampato-Sabancaya volcanic complex constructed since ~450ka until Holocene.•Ampato experienced a long, complex and variable eruptive activity, including several highly explosive events.•Sabancaya is a Holocene edifice roughly constructed since 10–6ka by effusive eruptions.•Late Holocene Sabancaya activity was characterised by medium-sized vulcanian events.•Magma output rates show important variations throughout the volcano's history.
Studies focusing on dietary pesticides in population-based samples are scarce and little is known about potential mixture effects. We aimed to assess associations between dietary pesticide exposure ...profiles and Type 2 Diabetes (T2D) among NutriNet-Santé cohort participants.
Participants completed a Food Frequency Questionnaire at baseline, assessing conventional and organic food consumption. Exposures to 25 active substances used in European Union pesticides were estimated using the Chemisches und Veterinäruntersuchungsamt Stuttgart residue database accounting for farming practices. T2D were identified through several sources. Exposure profiles were established using Non-Negative Matrix Factorization (NMF), adapted for sparse data. Cox models adjusted for known confounders were used to estimate hazard ratios (HR) and 95% confidence interval (95% CI), for the associations between four NMF components, divided into quintiles (Q) and T2D risk.
The sample comprised 33,013 participants aged 53 years old on average, including 76% of women. During follow-up (median: 5.95 years), 340 incident T2D cases were diagnosed. Positive associations were detected between NMF component 1 (reflecting highest exposure to several synthetic pesticides) and T2D risk on the whole sample: HR
= 1.47, 95% CI (1.00, 2.18). NMF Component 3 (reflecting low exposure to several synthetic pesticides) was associated with a decrease in T2D risk, among those with high dietary quality only (high adherence to French dietary guidelines, including high plant foods consumption): HR
= 0.31, 95% CI (0.10, 0.94).
These findings suggest a role of dietary pesticide exposure in T2D risk, with different effects depending on which types of pesticide mixture participants are exposed to. These associations need to be confirmed in other types of studies and settings, and could have important implications for developing prevention strategies (regulation, dietary guidelines).
This study is registered in ClinicalTrials.gov ( NCT03335644 ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We question the timing of continental breakup and early oceanization in Baffin Bay, North-East Atlantic. North of the Ungava fault zone, the breakup was syn-magmatic and led to the development of ...conjugate volcanic passive margins (VPMs). We investigated the innermost part of the W-Greenland VPM where a remarkable inner-SDR is fully exposed in the Svartenhuk area. Our new radiometric ages and paleomagnetic data from syn-tectonic basaltic lavas indicate that continental stretching and thinning spanned the C26r to, at least, the C24r period, giving an Eocene lower boundary age for continental breakup in Baffin Bay. These results contradict the proposed flooring of Baffin Bay by a Paleocene oceanic crust older than C24n and also question the accretion of oceanic crust before C22. We confront our results to the dynamics of the northward oceanic-rift propagation across the Ungava transform fault system, and we suggest that plate breakup in Baffin Bay occurred ~8 m.y. later than in N-Labrador Sea as a result of the thermal and mechanical barrier effect induced by the Ungava transform zone.
•Coupling of 40Ar/39Ar and unspiked KAr ages with paleomagnetic data•Dating of the West Greenland Volcanic Province in Svartenhuk Halvø•Dating of the syn-magmatic deformation of the West Greenland volcanic margin•Baffin Bay continental breakup is younger than Early Eocene (C24r)
The 40Ar/39Ar method was used to refine the dating of a volcanic sequence drilled in the Ko'olau volcano which recorded a period of anomalously shallow inclinations. Previously, this sequence was ...dated using the unspiked K-Ar method at ≈ 2.1 Ma (Laj et al., 2000). This age was questioned by Ozawa et al. (2005) based on unspiked K-Ar ages of 2.40 and 2.41 Ma for two stratigraphically younger lava flows. Our new 40Ar/39Ar isochron results date this period of low inclination between 2.52 ± 0.10 and 2.40 ± 0.17 Ma. The combination of our two most reliable ages allows us to propose an age of 2.46 ± 0.13 Ma for the magnetic anomaly that we attribute to the cryptochon C2r.2r-1. This age agrees with previous estimates on the Halawa section of 2.46 ± 0.12 Ma (Singer, 2014) and the São Gonçalo profile of 2.46 ± 0.08 Ma (Holm et al., 2008; Knudsen et al., 2009). Our 40Ar/39Ar ages confirm the unspiked K-Ar dating results of Ozawa et al. (2005), which were corrected for the mass-fractionation effect. Along with published data, our new ages permit to bracket the Makapuu late-shield stage between 2.6 and 2.2 Ma.
Living organisms display internal biological rhythms, which are an evolutionarily conserved adaptation to the environment that drives their rhythmic behavioral and physiological activities. The gut ...microbiota has been proposed, in association with diet, to regulate the intestinal peripheral clock. However, the effect of gut dysbiosis on liver remains elusive, despite that germfree mice show alterations in liver metabolic functions and the hepatic daily rhythm. We analyzed whether the disruption of gut microbial populations with various antibiotics would differentially impact liver functions in mice. Our results support the notion of an impact on the hepatic biological rhythm by gram-positive bacteria. In addition, we provide evidence for differential roles of gut microbiota spectra in xenobiotic metabolism that could protect against the harmful pharmacological effects of drugs. Our results underscore a possible link between liver cell proliferation and gram-positive bacteria.
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