Background
Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown.
Objective
To ...investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients.
Methods
We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen‐induced arthritis mouse model and 3T3‐L1 adipocytes treated with conditioned serum from RA patients.
Results
Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA‐induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients.
Conclusions
Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.
The nuclear protein high-mobility group box 1 (HMGB1) can be passively released by necrotic cells or secreted actively by several cell types to regulate immune and inflammatory responses, as well as ...tissue remodeling. We herein aimed to characterize the effect of insulin resistance on HMGB1 in adipose tissue and to examine its potential role as a metabolic regulator in β-pancreatic cells.
Plasma HMGB1 concentration and adipose HMGB1 expression were assessed in relation to obesity and insulin resistance. Cultured adipocytes from lean and obese patients were used to investigate the intracellular distribution and factors regulating HMGB1 release, as well as to test its effects on adipogenesis and lipid metabolism. A regulatory role for HMGB1 in insulin secretion was also investigated.
Circulating HMGB1 was positively associated with body mass index, while adipose HMGB1 mRNA levels correlated with the expression of inflammatory markers. Insulin resistance modified the intracellular distribution of HMGB1 in human adipocytes, with HMGB1 being predominantly nuclear in lean and obese normoglycemic individuals while localized to the cytosol in obese patients with type 2 diabetes. Adipocytes from lean individuals exposed to conditioned media from lipopolysaccharide-stimulated macrophages induced HMGB1 redistribution to the cytoplasm and release. HMGB1 treatment had no effect on differentiation and lipid metabolism in adipocytes. However, HMGB1, whose circulating levels correlated with postload insulin concentration, increased both insulin release and intracellular Ca(2+) concentration in INS-1 cells.
These findings show, for the first time, that HMGB1 expression and release by human adipocytes is altered by inflammatory conditions as those imposed by obesity and insulin resistance. Our data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion of β-pancreatic cells.
Discovery of the adipose tissue as a major source of signaling molecules almost three decades ago set a novel physiological paradigm that paved the way for the identification of metabolic organs as ...endocrine organs. Adipocytes, the main adipose tissue cell type, do not only represent the principal site of energy storage in form of triglycerides, but also produce a variety of molecules for short and long distance intercellular communication, named adipokines, which coordinate systemic responses. Although the best known adipokines identified and characterized hitherto are leptin and adiponectin, novel adipokines are continuously being described, what have significantly helped to elucidate the role of adipocyte biology in obesity and associated comorbidities. One of these novel adipokines is high-mobility group box 1 (HMGB1), a ubiquitous nuclear protein that has been recently reported to be dysregulated in obese dysfunctional adipocytes. Although the classical function of HMGB1 is related to inflammation and immunity, acting as an alarmin, novel advances evidence an active implication of HMGB1 in tissue remodeling and fibrosis. This review summarizes the current evidence on the mechanisms controlling HMGB1 release, as well as its role as a regulator of adipocyte function and extracellular matrix remodeling, with special emphasis on the potential of this novel adipokine as a target in the obesity treatment.
Agriculture represents about 11% of global anthropogenic greenhouse gas emissions (GHGe). Many climate change mitigation strategies have been evaluated in Mediterranean agroecosystems, including ...their soil organic carbon sequestration potential. High residue yielding old varieties could constitute a useful alternative, especially for organic farming, which lacks specific genetic material. In this study, old and modern wheat varieties were evaluated under organic (ORG) and conventional (CON) management during a 3-year field experiment under rainfed Mediterranean conditions. Field measurements of biomass components, literature emission factors, and soil organic carbon modeling were combined in an attributional Life Cycle Assessment, in order to estimate GHGe from “cradle to farm gate”. The resulting yield-based carbon footprints of old wheat varieties were significantly lower than those of modern varieties both under CON management, decreasing from 263 to 144 g CO2e kg−1, and under ORG management, decreasing from 29 to −43 g CO2e kg−1. Our results indicate that climate change mitigation strategies in Mediterranean rainfed cereal cropping systems should focus on diminishing GHGe from machinery and fertilizer use, and promoting carbon sequestration. The combination of organic management and old cereal varieties can constitute a promising climate change mitigation strategy in these systems, as low area-scaled GHGe of organic management are combined with enhanced carbon sequestration and a good yield performance of old varieties under these conditions.
•C footprint of old vs modern wheat under organic & conventional farming was studied.•Old wheat varieties promoted biomass production without decreasing yields.•The lowest C footprint was achieved by old wheat varieties under organic farming.•SOC balance contributed the most to the reduction of the C footprint.•Old wheat rainfed cultivation could be a useful climate change mitigation strategy.
The main limitations of lipidomics analysis are the chemical complexity of the lipids, the range of concentrations at which they exist, and the variety of samples usually analyzed. These limitations ...particularly affect the characterization of polar lipids owing to the interference of neutral lipids, essentially acylglycerides, which are at high concentration and suppress ionization of low concentrated lipids in mass spectrometry detection. The influence of sample preparation on lipidomics analysis of polar lipids in adipose tissue by LC–MS/MS was the aim of this research. Two common extractants used for lipids isolation, methanol:chloroform (MeOH:CHCl3) and methyl tert-butyl ether (MTBE), were qualitatively and quantitatively compared for the extraction of the main families of lipids. The obtained results showed that each family of lipids is influenced differently by the extractant used. However, as a general trend, the use of MTBE as extractant led to higher extraction efficiency for unsaturated fatty acids, glycerophospholipids and ceramides, while MeOH:CHCl3 favored the isolation of saturated fatty acids and plasmalogens. The implementation of a solid-phase extraction (SPE) step for selective isolation of glycerophospholipids prior to LC–MS/MS analysis was assayed to evaluate its influence on lipids detection coverage as compared to direct analysis. This step was critical to enhance the detection coverage of glycerophospholipids by removal of ionization suppression effects caused by acylglycerides.
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•Sample preparation has been studied in the analysis of polar lipids in adipose tissue.•The matrix used in this research was human visceral adipose tissue.•The study was performed by an untargeted LC–QTOF MS/MS approach.
•Cover crops increased total, unprotected and protected top 5 cm SOC contents.•Cover crops reduced the sediment yield by 11.5 Mg ha-1 yr-1 compared to bare soils.•Cover crops reduced the loss of SOC ...by 74 kg C ha-1 yr-1 compared to bare soils.•Neither CC nor CT promoted a preferential loss of a particular Corg fraction.•Searching for CC plant species of fast-growing short life-cycle is necessary.
Soil erosion plays an important role in C cycling at farm scale, especially in bare soil areas. In Mediterranean woody crops, temporary cover crops (CC) effectively reduce soil erosion and increase total and protected soil organic carbon (SOC) fractions. However, the effects of CC in olive groves on the preferential loss of organic carbon (Corg) fractions remains poorly understood. To address this issue, in four plots with seeded CC and two tilled plots (CT) in a Spanish olive grove, the unprotected and protected Corg fractions were measured in soil and sediments over the course of a hydrological year. The sediment/soil C enrichment ratios (ERSOC) were calculated, and results analysed considering the rainfall regimes of the site: dry (DS), heavy-rainy (HRS) and rainy (RS). Total, unprotected and protected Corg contents in the top 5 cm soil of CC plots were 46 %, 88.4 % and 28.5 %, respectively, higher than those of CT. 79.7 % and 70.3 % of the annual sediment yield (SY) was collected during December in CC and CT plots, respectively. Soil loss in CC plots (x¯ = 9.2 Mg ha–1 yr–1) was significantly lower (−55.6 %) than that in CT plots. Despite that the average eroded Corg was higher in the CT (x¯ = 222 kg C ha–1 yr–1) compared to CC (x¯ = 148 kg C ha–1 yr–1) plots differences were not significant due to the higher Corg concentration in the sediment from CC plots. The highest proportion of eroded Corg (44%–45%) corresponded to the physically protected fraction. The highest ERSOC (1.99 and 2.04 for CC and CT, respectively) was recorded in DS whereas the lowest was in the RS (0.90) and HRS (0.96) seasons. The mean ERSOC were of 1.00 and 0.92 in the CC and CT plots, with no significant difference. The fact that most of the SY was recorded in one month, when CC plants were not fully developed, might explain the ERSOC at 1, and why their presence did not modify it. This study demonstrates that CC favours greater total, unprotected and protected Corg fractions in the topsoil, promoting soil C sequestration. The asynchrony between the periods of full development of the CC plants and those with the highest rainfall erosivity prevented any selectiveness of the eroded Corg. Thus, fast-growing CC plant species with short life-cycles are recommended, as well as adequate management to promote self-seeding avoiding soil disturbance for seeding in erosion prone seasons.
Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is increasingly recognized for its potential in the discovery of novel biomarkers directly from tissue sections. ...However, there are no MALDI IMS studies as yet on the adipose tissue, a lipid-enriched tissue that plays a pivotal role in the development of obesity-associated disorders. Herein, we aimed at developing an optimized method for analyzing adipose tissue lipid composition under both physiological and pathological conditions by MALDI IMS. Our studies showed an exacerbated lipid delocalization from adipose tissue sections when conventional strategies were applied. However, our optimized method using conductive-tape sampling and 2,5-dihydroxybenzoic acid (DHB) as a matrix, preserved the anatomical organization and minimized lipid diffusion from sample sections. This method enabled the identification of a total of 625 down-regulated and 328 up-regulated m/z values in the adipose tissue from a rat model of extreme obesity as compared to lean animals. Combination of MALDI IMS and liquid chromatography (LC)-MS/MS data identified 44 differentially expressed lipid species between lean and obese animals, including phospholipids and sphingomyelins. Among the lipids identified, SM(d18:0_18:2), PE(P-16:0_20:0), and PC(O-16:0_16:1) showed a differential spatial distribution in the adipose tissue of lean vs. obese animals. In sum, our method provides a valuable new tool for research on adipose tissue that may pave the way for the identification of novel biomarkers of obesity and metabolic disease.
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•Conventional matrix deposition induced lipid diffusion in adipose tissue sections.•Conductive-tape sampling and DHB reduced adipose tissue lipid delocalization.•MALDI IMS revealed 625 down- and 328 up-regulated m/z values linked to obesity.•MALDI IMS revealed obesity-related differences in adipose tissue lipid distribution.
•Toxic effects of the combination of carbon nanotubes and nonylphenol are examined.•No generalized evidences of synergistic toxicity were reported for most conditions.•More stable dispersions of ...nanoparticles were achieved by adding serum to the medium.•The serum increased the tolerance of 3T3-L1 cells to all treatments tested.•Intracellular distribution of nanoparticles was analyzed by Raman spectroscopy.
The aim of this study was to assess the toxicological risks arising from the coexistence of polyethylene glycol coated single-walled carbon nanotubes (SWCNTs-PEG) and a known environmental contaminant: 4-nonylphenol (NP). To this end, in vitro toxicity assays involving the exposure of 3T3-L1 cells (mouse embryonic fibroblasts) to SWCNTs-PEG alone or in combination with NP for 24 or 48h were performed. Experimental treatments were conducted in both presence (10%) and absence of serum in order to evaluate its influence on the toxicity of SWCNTs-PEG. Although the results provided no unambiguous evidences of synergistic toxicity between SWCNTs-PEG and NP, some specific treatments with mixtures (SWCNTs-PEG+NP) resulted in an unexpected combined toxicity in relation to the individual treatments. Only in those cases the interaction between SWCNTs-PEG and NP could have a synergistic effect on the resulting toxicity. The addition of 10% serum increased the stability of SWCNTs-PEG in the culture medium—possibly by steric repulsions—and reduced the toxicity of nanoparticles as a result. Overall, the serum had a “protective effect” on cells against all treatments: SWCNTs-PEG, NP or their mixtures (SWCNTs-PEG+NP). Raman spectroscopy allowed the intracellular distribution of SWCNTs-PEG to be elucidated.
Since the 1980s, 3 major hurricanes have made landfall on Puerto Rico: Hugo in September 1989 (Saffir-Simpson scale, category 4), Georges in September 1998 (category 3) and María in September 2017 ...(category 4). María was the most devastating hurricane since the 3 major hurricanes that occurred in 1899- 1932. Major hurricanes can cause severe abundance declines and population bottlenecks by decreasing survival and reproductive rates and increasing predation and competition for limited resources. In April to June 1986-2021, we used distance sampling to estimate abundance and monitor the population dynamics of the endangered Puerto Rico plain pigeon
Patagioenas inornata wetmorei
and the abundant scaly-naped pigeon
P
.
squamosa
and red-tailed hawk
Buteo jamaicensis
. Here, we fit a Bayesian state-space logistic model with distance sampling abundance estimates to generate posterior estimates of maximum population growth rate and population carrying capacity, and predict abundance in April to June 2020-2030. In addition, we used
N
-mixture and 2-species models to assess association patterns in April to June 2015-2019. The scaly-naped pigeon and red-tailed hawk populations did not decline, or recovered faster from their declines than the plain pigeon population after the hurricanes. The association patterns between species were positive but variable for the 2 pigeon species and negative but variable for the plain pigeon and red-tailed hawk. At lowered abundance (i.e. mean ± SE estimates
N̂
= 1043 ± 476 island-wide and
N̂
= 522 ± 157 at the centre of abundance in the east-central region in April to June 2018-2021), the plain pigeon may become extinct if another hurricane with the path and intensity of María makes landfall on the island during the current decade.
Among the main innovations in olive growing, the conversion of cultivation practices towards organic agriculture stands out. Since the organic crops are subject to the granting of economic subsidies ...by the Spanish Ministry of Agriculture, this has given rise to fraudulent situations, masking the use of conventional pesticides in "fake organic" crops. To investigate alternative methods, complementary to analytical chemists that can provide reliable information to discerning organic crops from those subjects to synthetic pesticides is the aim of this research. A new technique is being developed, based on the induction of sublethal effects on the beneficial insects, through the experimental application of a commercial insecticide on a small scale, in the target crop. The effect triggered by the insecticide can be monitored by means of a yellow sticky trap device, installed for each olive tree, which allows to observe deviations in its capture rate from what occurs in the absence of insecticide (control) and finally verifying if the populations of beneficial insects affected in the olive grove, whether or not they are accustomed to the toxic action of the insecticide. Obviously, in order to maintain environmental integrity in the supposed ecological target olive groves, this induction test should be applied on the smallest scale as possible, thus reducing the application area of the pesticide, which implies adjusting the sample size to a minimum, maintaining an acceptable reliability in the estimates. During the autumn of 2017, six plots of 7x7 configuration were selected in an olive grove in the province of Jaén (southern Spain), three of these were treated with Dimethoate, while the remaining were considered as control. After the treatment application, sticky yellow traps were installed (one in each of the olive trees), thus allowing a maximum of 49 repetitions per plot. Among the identified beneficial insects, the most abundant species was Aeolothrips intermedius. Taking this species as a reference, the results indicate that the differences between treated and control parcel were statistically significant from a minimum sample size of 17 replications onwards. In coincidence with the above, the results have allowed determining that the minimum size of the experimental target plot, to obtain acceptable population estimates (relative error of up to 10%), would require a minimum area of at least 100 m2, representing a minimum number of 17 olive trees. These results provide a reasonable statistical basis for suitably adapting the methodology that allows acceptable estimates, therefore, the application of this methodology of detection of organic crops would require a very small area, equivalent to a practically insignificant number of olive trees, so it would not compromise the ecological quality of the target plantation.
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