Adipose Tissue Concentrations Research Articles

Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective.

Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2-3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.

Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial-Mesenchymal Transition Process.

We aimed to explore the relationship of adipose tissue concentrations of some persistent organic pollutants (POPs) with the risk of endometriosis and the endometriotic tissue expression profile of genes related to the endometriosis-related epithelial-mesenchymal transition (EMT) process. This case-control study enrolled 109 women (34 cases and 75 controls) between January 2018 and March 2020. Adipose tissue samples and endometriotic tissues were intraoperatively collected to determine concentrations of nine POPs and the gene expression profiles of 36 EMT-related genes, respectively. Associations of POPs with endometriosis risk were explored with multivariate logistic regression, while the relationship between exposure and gene expression profiles was assessed through Spearman correlation or Mann-Whitney U tests. After adjustment, increased endometriosis risk was associated with p,p'-DDT, PCB-180, and ΣPCBs. POP exposure was also associated with reduced gene expression levels of the CLDN7 epithelial marker and increased levels of the ITGB2 mesenchymal marker and a variety of EMT promoters (HMGA1, HOXA10, FOXM1, DKK1, CCR1, TNFRSF1B, RRM2, ANG, ANGPT1, and ESR1). Our findings indicate that exposure to POPs may increase the risk of endometriosis and might have a role in the endometriosis-related EMT development, contributing to the disease onset and progression. Further studies are warranted to corroborate these findings.

Integrative model-based comparison of target site-specific antimicrobial effects: A case study with ceftaroline and lefamulin

ObjectivePredictions of antimicrobial effects typically rely on plasma-based pharmacokinetic-pharmacodynamic (PK-PD) targets, ignoring target-site concentrations and potential differences in tissue penetration between antibiotics. In this study, we applied PK-PD modelling to compare target site-specific effects of antibiotics by integrating clinical microdialysis data, in vitro time-kill curves, and antimicrobial susceptibility distributions. As a case study, we compared the effect of lefamulin and ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) at soft-tissue concentrations. MethodsA population PK model describing lefamulin concentrations in plasma, subcutaneous adipose and muscle tissue was developed. For ceftaroline, a similar previously reported PK model was adopted. In vitro time-kill experiments were performed with six MRSA isolates and a PD model was developed to describe bacterial growth and antimicrobial effects. The clinical PK and in vitro PD models were linked to compare antimicrobial effects of ceftaroline and lefamulin at the different target sites. ResultsConsidering minimum inhibitory concentration (MIC) distributions and standard dosages, ceftaroline showed superior anti-MRSA effects compared to lefamulin both at plasma and soft-tissue concentrations. Looking at the individual antibiotics, lefamulin effects were highest at soft-tissue concentrations, while ceftaroline effects were highest at plasma concentrations, emphasising the importance of considering target-site PK-PD in antibiotic treatment optimisation. ConclusionGiven standard dosing regimens, ceftaroline appeared more effective than lefamulin against MRSA at soft-tissue concentrations. The PK-PD model-based approach applied in this study could be used to compare or explore the potential of antibiotics for specific indications or in populations with unique target-site PK.

Influence of Different Plant Extracts on CYP-Mediated Skatole and Indole Degradation in Pigs.

One of the primary substances responsible for the unpleasant odor in boar meat is skatole. Enzymes belonging to the cytochrome P450 (CYP) family play a pivotal role in the hepatic clearance of skatole. This study aimed to investigate the impact of oregano essential oil (OEO), Schisandra chinensis extract (SC), and garlic essential oil (GEO) on hepatic CYP2E1 and CYP2A activity in pigs. In three consecutive trials, cannulated castrated male pigs were provided with a diet containing 0.2-0.3% of one of these plant extracts. Following a 14-day feeding period, the animals were slaughtered, and liver and fat samples were collected. The findings indicate that the activities of CYP2E1 were unaffected by any treatment. However, GEO treatment demonstrated a significant reduction in CYP2A activity (p < 0.05). Pigs treated with GEO also exhibited a notable increase in skatole concentrations in both plasma and adipose tissue. In contrast, animals fed SC displayed elevated skatole concentrations in plasma but not in fat tissue. OEO did not influence skatole concentrations in either blood or fat. Furthermore, the study revealed that a supplementation of 6 g GEO per animal per day induced a significant increase in skatole concentrations in blood plasma within 24 h.

Accumulation of organophosphorus pollutants in adipose tissue of obese women - metabolic alterations

Organophosphorus pesticides (OPPs) and organophosphate esters (OPEs) are organophosphorus compounds created as substitutes for persistent environmental pollutants, namely organochlorines pesticides and brominated flame retardants, respectively. However, there is evidence that organophosphorus compounds are also widespread across the environment and have adverse effects on biota. In humans, OPPs and OPEs were reported to be carcinogenic, neurotoxic, hepatotoxic, nephrotoxic, amongst others. As lipophilic compounds, these accumulate in fat tissues as adipose tissue. Yet biomonitoring studies and analytical methodologies to assess these compounds in the human body are scarce, particularly in adipose tissue. In this study, the presence of six OPPs and seven OPEs was determined in samples of subcutaneous adipose tissue (scAT) and visceral adipose tissue (vAT) from 188 adult obese women. OPPs and OPEs were quantified by gas chromatography (GC) flame photometric detection and confirmed in GC tandem mass spectrometry. The detection frequencies ranged between 0.5-1.6% and 48–53%, respectively for OPPs and OPEs. Organophosphorus pollutants were present in both adipose tissues and median concentrations were 0.008 ± 0.020 μg/g scAT and 0.009 ± 0.020 μg/g vAT. A total of 32 Spearman's correlations were found between organophosphorus pollutants concentrations in adipose tissue and several biochemical parameters (18 positive and 14 negative). Our results show that anthropometric and hormonal parameters, cholesterol, glycaemia, macrominerals, urea and sedimentation velocity might be influenced by the presence of these compounds. The presence of organophosphorus pollutants in the environmental and their possible effect on female metabolic processes is concerning. Particularly because presently OPEs usage is not controlled or limited by any regulation. More studies are needed to fully understand these pollutants behaviour and hazard effects on human health, biota, and the environment so control regulations can be drawn to prevent and lessen their effects.

Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse

Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450 activity, impairing the ability of insects to detoxify insecticides. PBO was recently discovered to also inhibit Sonic hedgehog signaling, a pathway required for embryonic development, and rodent studies have demonstrated the potential for in utero PBO exposure to cause structural malformations of the brain, face, and limbs, or more subtle neurodevelopmental abnormalities. The current understanding of the pharmacokinetics of PBO in mice is limited, particularly with respect to dosing paradigms associated with developmental toxicity. To establish a pharmacokinetic (PK) model for oral exposure, PBO was administered to female C57BL/6J mice acutely by oral gavage (22–1800 mg/kg) or via diet (0.09 % PBO in chow). Serum and adipose samples were collected, and PBO concentrations were determined by HPLC-MS/MS. The serum concentrations of PBO were best fit by a linear one-compartment model. PBO concentrations in visceral adipose tissue greatly exceeded those in serum. PBO concentrations in both serum and adipose tissue decreased quickly after cessation of dietary exposure. The elimination half-life of PBO in the mouse after gavage dosing was 6.5 h (90 % CI 4.7–9.5 h), and systemic oral clearance was 83.3 ± 20.5 mL/h. The bioavailability of PBO in chow was 41 % that of PBO delivered in olive oil by gavage. Establishment of this PK model provides a foundation for relating PBO concentrations that cause developmental toxicity in the rodent models to Sonic hedgehog signaling pathway inhibition.

Sex Differences in Plasma, Adipose Tissue, and Central Accumulation of Cannabinoids, and Behavioral Effects of Oral Cannabis Consumption in Male and Female C57BL/6 Mice.

Cannabis edibles are an increasingly popular form of cannabis consumption. Oral consumption of cannabis has distinct physiological and behavioral effects compared with injection or inhalation. An animal model is needed to understand the pharmacokinetics and physiological effects of oral cannabis consumption in rodents as a model for human cannabis edible use. Adult male and female C57BL/6 mice received a single dose of commercially available cannabis oil (5 mg/kg Δ⁹-tetrahydrocannabinol [THC]) by oral gavage. At 0.5, 1, 2, 3, and 6 hours post exposure, plasma, hippocampus, and adipose tissue were collected for THC, 11-OH-THC, and THC-COOH measures. We report delayed time to peak THC and 11-OH-THC concentrations in plasma, brain, and adipose tissue, which is consistent with human pharmacokinetics studies. We also found sex differences in the cannabis tetrad: (1) female mice had a delayed hypothermic effect 6 hours post consumption, which was not present in males; (2) females had stronger catalepsy than males; (3) males were less mobile following cannabis exposure, whereas female mice showed no difference in locomotion but an anxiogenic effect at 3 hours post exposure; and (4) male mice displayed a longer-lasting antinociceptive effect of oral cannabis. Oral cannabis consumption is a translationally relevant form of administration that produces similar physiological effects as injection or vaping administration and thus should be considered as a viable approach for examining the physiological effects of cannabis moving forward. Furthermore, given the strong sex differences in metabolism of oral cannabis, these factors should be carefully considered when designing animal studies on the effects of cannabis.

Evidence for an accumulation of mineral oil saturated hydrocarbons (MOSH) in human tissues: a re-evaluation of biopsy and autopsy data

AbstractConsumers are exposed to mineral oil hydrocarbons (MOH) e.g. through foodstuffs and cosmetics. Upon ingestion, MOH follow the absorption pathway of dietary lipids. Analytical chemistry has revealed the presence of the main fraction, designated as mineral oil saturated hydrocarbons (MOSH), in mesenteric lymph nodes (MLNs), liver, spleen, and adipose tissue. Recent results from animal studies raised concerns about a long-term, possibly irreversible accumulation of some MOSH in humans. To address this issue, we performed a statistical re-analysis of published biopsy and autopsy data regarding the age-dependence of MOSH levels in human tissue. MOSH concentrations in MLNs and adipose tissue showed a 1.2–1.4-fold increase per decade, pointing to very long-term accumulation in both tissues. There was no evidence for age-dependent MOSH concentrations in liver and spleen. There was no sex difference in the MOSH concentrations in MLNs, suggesting a similar oral exposure for men and women. On average, women had a 2.2–2.5-fold higher MOSH concentration in the liver, spleen and adipose tissue compared to men. This finding may point to a sex difference in metabolism, in line with animal data. The use of certain cosmetics was a relevant predictor in addition to age. Women that used cosmetics like lipstick, hand cream, and sun cream had an average 2.1-fold higher MOSH concentration in abdominal subcutaneous fat than non-users.

Sialic acids Neu5Ac and KDN in adipose tissue samples from individuals following habitual vegetarian or non-vegetarian dietary patterns

Sialic acids (Sias) are a class of sugar molecules with a parent nine-carbon neuraminic acid, generally present at the ends of carbohydrate chains, either attached to cellular surfaces or as secreted glycoconjugates. Given their position and structural diversity, Sias modulate a wide variety of biological processes. However, little is known about the role of Sias in human adipose tissue, or their implications for health and disease, particularly among individuals following different dietary patterns. The goal of this study was to measure N-Acetylneuraminic acid (Neu5Ac), N-Glycolylneuraminic acid (Neu5Gc), and 2-keto-3-deoxy-d-glycero-d-galacto-nononic acid (KDN) concentrations in adipose tissue samples from participants in the Adventist Health Study-2 (AHS-2) and to compare the abundance of these Sias in individuals following habitual, long-term vegetarian or non-vegetarian dietary patterns. A method was successfully developed for the extraction and detection of Sias in adipose tissue. Sias levels were quantified in 52 vegans, 56 lacto-vegetarians, and 48 non-vegetarians using LC–MS/MS with Neu5Ac-D-1,2,3-13C3 as an internal standard. Dietary groups were compared using linear regression. Vegans and lacto-ovo-vegetarians had significantly higher concentrations of Neu5Ac relative to non-vegetarians. While KDN levels tended to be higher in vegans and lacto-ovo-vegetarians, these differences were not statistically significant. However, KDN levels were significantly inversely associated with body mass index. In contrast, Neu5Gc was not detected in human adipose samples. It is plausible that different Neu5Ac concentrations in adipose tissues of vegetarians, compared to those of non-vegetarians, reflect a difference in the baseline inflammatory status between the two groups. Epidemiologic studies examining levels of Sias in human adipose tissue and other biospecimens will help to further explore their roles in development and progression of inflammatory conditions and chronic diseases.

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

Maternal High-Fat Diet Consumption in Sprague Dawley Rats Compromised the Availability and Altered the Tissue Distribution of Lutein in Neonatal Offspring.

Lutein, the most abundant carotenoid in the infant eye and brain, is critical for their visual and cognitive development. Due to its lipophilic nature, a high adiposity may affect the tissue distribution of lutein. The aim of the study was to determine the impacts of a maternal high-fat diet (HFD) consumption on the status of lutein in the neonatal offspring. Female Sprague Dawley rats (n = 6) were fed a normal fat diet (NFD) or a HFD for 8 weeks before mating, and they were switched to an NFD or an HFD containing the same concentration of lutein ester during gestation and lactation. Rat pups (n = 7/group/time) were euthanized on postnatal day 2 (P2), P6, P11, and P20 for measuring tissue lutein concentrations. No significant difference in maternal lutein intake was found between the two groups. At both P6 and P11, a significantly lower lutein concentration was noted in the milk samples separated from the stomach of HFD pups than the concentration in the samples from the NFD pups; the HFD group showed a significantly lower lutein concentration in the liver. At P11, the HFD pups exhibited a significantly lower lutein concentration in the eye, brain, and brown adipose tissue accompanied with a significantly higher lutein concentration and mass in the visceral white adipose tissue. The study was the first to provide evidence that maternal HFD consumption resulted in a compromised availability and altered distribution of lutein in the neonatal offspring.

Ovariectomy Increases Circulating Retinol-Binding Protein Concentrations Independently of Sex-Dependent Differences in Retinol Concentrations in Rats

BackgroundThere is a sex-dependent difference in blood retinol and RBP concentrations, and plasma RBP is associated with insulin resistance. ObjectivesWe aimed to clarify sex-dependent variations in body concentrations of retinol and RBPs and their association with sex hormones in rats. MethodsPlasma and liver retinol concentrations and hepatic mRNA and plasma concentrations of RBP4 were analyzed in 3- and 8-wk-old male and female Wistar rats before and after sexual maturity (experiment 1) and in orchiectomized male Wistar rats (experiment 2) and ovariectomized female Wistar rats (experiment 3). Furthermore, the mRNA and protein concentrations of RBP4 in adipose tissue were measured in ovariectomized female rats (experiment 3). ResultsThere were no sex-dependent differences in liver retinyl palmitate and retinol concentrations; however, the plasma retinol concentration was significantly higher in male rats than that in female rats after sexual maturity. Furthermore, the plasma retinol concentrations did not differ between the ovariectomized or orchiectomized rats and the control rats. Plasma Rbp4 mRNA concentrations were higher in male rats than those in female rats but not in castrated and control rats, a change consistent with plasma retinol concentration. Plasma RBP4 concentrations were also higher in male rats than those in female rats; however, unlike liver Rbp4 gene expression, plasma RBP4 concentrations were 7-fold higher in the ovariectomized rats than those in the control rats. Moreover, the Rbp4 mRNA concentrations in inguinal white adipose tissue was significantly higher in the ovariectomized rats than those in the control rats and correlated with plasma RBP4 concentrations. ConclusionsHepatic Rbp4 mRNA is higher in male rats through a sex hormone–independent mechanism, which may contribute to sex differences in blood retinol concentrations. Furthermore, ovariectomy leads to an increase in adipose tissue Rbp4 mRNA and blood RBP4 concentrations, which may contribute to insulin resistance in ovariectomized rats and postmenopausal women.

Testosterone and persistent organic pollutants in East Greenland male polar bears (Ursus maritimus)

Legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) are chemicals that undergo long-range transport to the Arctic. These chemicals possess endocrine disruptive properties raising concerns for development and reproduction. Here, we report the relationship between concentrations of testosterone (T) and persistent organic pollutant (POPs) in 40 East Greenland male polar bears (Ursus maritimus) sampled during January to September 1999–2001. The mean ± standard concentrations of blood T were 0.31 ± 0.49 (mean ± SD) ng/mL in juveniles/subadults (n = 22) and 3.58 ± 7.45 ng/mL in adults (n = 18). The ∑POP concentrations (mean ± SD) in adipose tissue were 8139 ± 2990 ng/g lipid weight (lw) in juveniles/subadults and 11,037 ± 3950 ng/g lw in adult males, respectively, of which Σpolychlorinated biphenyls (ΣPCBs) were found in highest concentrations. The variation in T concentrations explained by sampling date (season), biometrics and adipose tissue POP concentrations was explored using redundancy analysis (RDA). The results showed that age, body length, and adipose lipid content in adult males contributed (p = 0.02) to the variation in POP concentrations. However, although some significant relationships between individual organochlorine contaminants and T concentrations in both juveniles/subadults and adult polar bears were identified, no significant relationships (p = 0.32) between T and POP concentrations were identified by the RDAs. Our results suggest that confounders such as biometrics and reproductive status may mask the endocrine disruptive effects that POPs have on blood T levels in male polar bears, demonstrating why it can be difficult to detect effects on wildlife populations.

Predictive Performance of Physiologically Based Pharmacokinetic Modelling of Beta-Lactam Antibiotic Concentrations in Adipose, Bone, and Muscle Tissues.

Physiologically based pharmacokinetic (PBPK) models consist of compartments representing different tissues. As most models are only verified based on plasma concentrations, it is unclear how reliable associated tissue profiles are. This study aimed to assess the accuracy of PBPK-predicted beta-lactam antibiotic concentrations in different tissues and assess the impact of using effect site concentrations for evaluation of target attainment. Adipose, bone, and muscle concentrations of five beta-lactams (piperacillin, cefazolin, cefuroxime, ceftazidime, and meropenem) in healthy adults were collected from literature and compared with PBPK predictions. Model performance was evaluated with average fold errors (AFEs) and absolute AFEs (AAFEs) between predicted and observed concentrations. In total, 26 studies were included, 14 of which reported total tissue concentrations and 12 unbound interstitial fluid (uISF) concentrations. Concurrent plasma concentrations, used as baseline verification of the models, were fairly accurate (AFE: 1.14, AAFE: 1.50). Predicted total tissue concentrations were less accurate (AFE: 0.68, AAFE: 1.89). A slight trend for underprediction was observed but none of the studies had AFE or AAFE values outside threefold. Similarly, predictions of microdialysis-derived uISF concentrations were less accurate than plasma concentration predictions (AFE: 1.52, AAFE: 2.32). uISF concentrations tended to be overpredicted and two studies had AFEs and AAFEs outside threefold. Pharmacodynamic simulations in our case showed only a limited impact of using uISF concentrations instead of unbound plasma concentrations on target attainment rates. The results of this study illustrate the limitations of current PBPK models to predict tissue concentrations and the associated need for more accurate models. SIGNIFICANCE STATEMENT: Clinical inaccessibility of local effect site concentrations precipitates a need for predictive methods for the estimation of tissue concentrations. This is the first study in which the accuracy of PBPK-predicted tissue concentrations of beta-lactam antibiotics in humans were assessed. Predicted tissue concentrations were found to be less accurate than concurrent predicted plasma concentrations. When using PBPK models to predict tissue concentrations, this potential relative loss of accuracy should be acknowledged when clinical tissue concentrations are unavailable to verify predictions.

Evaluation of the usefulness of determining the level of selected inflammatory biomarkers and resistin concentration in perivascular adipose tissue and plasma for predicting postoperative atrial fibrillation in patients who underwent myocardial revascularisation

BackgroundThe development of coronary artery disease (CAD) is related to the impaired quantity and composition of inflammatory proteins found in plasma and tissue, such as interleukin 6 (IL-6), adipokines, and resistin. Therefore, the level of plasma resistin in patients with advanced CAD could be indicative of the condition of epicardial adipose tissue and thus have an impact on the frequency and severity of postoperative complications in the form of paroxysmal atrial fibrillation.MethodsThe study included 108 patients who qualified for elective coronary artery bypass grafting (CABG) surgery from 2017 to 2020 and were categorized into two groups. The first group consisted of patients who developed atrial fibrillation in the postoperative period – the AF group, and the second group included patients who did not have arrhythmia – the non-AF group. The analysis incorporates the history, course of treatment, anthropometric characteristics of the test subjects, biochemical laboratory tests, and echocardiography. Perivascular adipose tissue (PVAT) sections were surgically harvested from the area of the left coronary trunk.ResultsThe resistin levels in the PVAT were significantly higher in the AF group than in the non-AF group (P = 0.000015). Similarly, plasma resistin levels increased significantly in the AF group compared to the non-AF group (P = 0.044). The values of other analyzed variables were not significantly different (analysis performed using the Mann–Whitney U test). Spearman’s rank-order correlation technique found a correlation between resistin in PVAT and plasma (r = 0.5933; P < 0.0001) in the whole study group, as well as in the AF group (r = 0.4782; P = 0.021) and the non-AF group (r = 0.4938; P < 0.0001). A correlation arose between the level of resistin in PVAT and the level of hsCRP (r = 0.3463; P = 0.005) in the whole study group and the non-AF group (r = 0.4448; P = 0.0011); however, no such correlation appeared in the AF group (r = 0.3076; P = 0.306).ConclusionsElevated levels of plasma resistin, which reflect PVAT resistin levels in patients qualified for myocardial revascularisation, may be associated with postoperative atrial fibrillation complications.

GPR120 Gene expression and activity in subcutaneous and intramuscular adipose tissues of Angus crossbred steers.

We hypothesized that media long-chain fatty acids (LCFA) would more greatly depress cyclic adenosine monophosphate (cAMP), glycerol, and free fatty acid (FFA) concentrations in subcutaneous (s.c.) adipose tissue than in intramuscular (i.m.) adipose tissue via G protein-coupled receptor 120 (GPR120). The GPR120 receptor binds to LCFA, which reduces cAMP production, thereby causing a depression in lipolysis. Fresh ex vivo explants of s.c. and i.m. adipose tissue from the fifth to eighth longissimus thoracic rib muscle section of 8, 22-mo-old Angus crossbred steers were transferred immediately to 6-well culture plates containing 3 mL of Krebs-Henseleit buffer/Hepes/5 mM glucose. Samples were preincubated with 0.5 mM theophylline plus 10 μM forskolin for 30 min, after which increasing concentrations of acetate or propionate (volatile fatty acids, VFA) (0, 1, 5, and 10 mM) in the absence or presence of 100 µM oleate (18:1n-9) or 100 μM palmitate (16:0) (LCFA) were added to the incubation media and incubated an additional 30 min. Main effects of adipose tissue depot (i.m. vs. s.c) and VFA (acetate vs. propionate) for adipose tissue concentrations of forskolin-stimulated cAMP were P = 0.747 and P = 0.106, respectively. The addition of LCFA to the media depressed adipose tissue concentrations of cAMP (P = 0.006) (LCFA main effects). The Tissue × VFA × LCFA interaction was not significant for any dependent variable (P ≥ 0.872). Therefore, concentrations of cAMP, glycerol, and FFA were analyzed separately for i.m. and s.c. adipose tissue by split-plot analysis. Concentrations of cAMP, glycerol, or FFA in i.m. and s.c. adipose tissue were not affected by increasing concentrations of VFA (P ≥ 0.497). Media LCFA had no effect on i.m. adipose tissue cAMP (P = 0.570) or glycerol (P = 0.470) but depressed i.m. adipose tissue FFA (P < 0.001). In s.c. adipose tissue, LCFA decreased concentrations of cAMP (P = 0.042) and glycerol (P = 0.038), but increased FFA concentration (P = 0.026). Expression of GPR120 (P = 0.804) and stearoyl-CoA desaturase (P = 0.538) was not different between s.c. adipose tissue and i.m. adipose tissue. The binding of VFA to the GPR43 receptor depresses cAMP production, thereby attenuating lipolysis, but GPR43 mRNA was undetectable in those adipose tissue samples. These results provide evidence for functional GPR120 receptors in s.c. adipose tissue but question the role of GPR43 in the accumulation of adipose tissue lipids in growing steers.

Fish Fingerprinting: Identifying Crude Oil Pollutants using Bicyclic Sesquiterpanes (Bicyclanes) in the Tissues of Exposed Fish.

In the present study, we investigated the possibility of identifying the source oils of exposed fish using ratios of bicyclic sesquiterpane (bicyclane) chemical biomarkers. In the event of an oil spill, identification of source oil(s) for assessment, or for litigation purposes, typically uses diagnostic ratios of chemical biomarkers to produce characteristic oil "fingerprints." Although this has been applied in identifying oil residues in sediments, water, and sessile filtering organisms, so far as we are aware this has never been successfully demonstrated for oil-exposed fish. In a 35-day laboratory trial, juvenile Lates calcarifer (barramundi or Asian seabass) were exposed, via the diet (1% w/w), to either a heavy fuel oil or to Montara, an Australian medium crude oil. Two-dimensional gas chromatography with high-resolution mass spectrometry and gas chromatography-mass spectrometry were then used to measure selected ratios of the bicyclanes to examine whether the ratios were statistically reproducibly conserved in the fish tissues. Six diagnostic bicyclane ratios showed high correlation (r2 > 0.98) with those of each of the two source oils. A linear discriminatory analysis model showed that nine different petroleum products could be reproducibly discriminated using these bicyclane ratios. The model was then used to correctly identify the bicyclane profiles of each of the two exposure oils in the adipose tissue extracts of each of the 18 fish fed oil-enriched diets. From our initial study, bicyclane biomarkers appear to show good potential for providing reliable forensic fingerprints of the sources of oil contamination of exposed fish. Further research is needed to investigate the minimum exposure times required for bicyclane bioaccumulation to achieve detectable concentrations in fish adiposetissues and to determine bicyclane depuration rates once exposure to oil has ceased. Environ Toxicol Chem 2023;42:7-18. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Persistent organochlorine pesticides in periprostatic adipose tissue from men with prostate cancer: Ethno-geographic variations, association with disease aggressiveness

Although several studies have examined the relationship between organochlorine pesticides (OCPs) and prostate cancer (PCa) risk, no data are available concerning the association between OCPs concentrations in periprostatic adipose tissue (PPAT), which reflects cumulative exposure, and PCa aggressiveness. Moreover, no previous study has compared OCPs exposure in two distinct ethno-geographical populations. The objectives were to analyze OCPs in PPAT of PCa patients from either Mainland France or French West Indies in correlation with features of tumor aggressiveness, after adjusting for potential confounders such age, BMI, and polyunsaturated fatty acid (PUFA) content of PPAT.PPAT was analyzed in 160 patients (110 Caucasians and 50 African-Caribbeans), 80 with an indolent tumor (ISUP group 1 + pT2), and 80 with an aggressive tumor (ISUP group more than 3 + pT3). The concentrations of 29 OCPs were measured in PPAT concomitantly with the characterization of PUFA content.Exposure patterns of OCPs differed according to the ethno-geographical origin. Most OCPs were found at higher concentration in Caucasian patients, whereas pp’-DDE content was twice as high in African-Caribbeans. Chlordecone was only detected in PPAT from African-Caribbean patients. Most OCP concentrations were positively correlated with age, and some with BMI. After adjusting for age, BMI, and PUFA composition of PPAT, no significant association was found between OCPs content and risk of aggressive disease, except of mirex which appeared inversely associated with aggressive features of PCa in Caucasian patients.These results highlight a significant ethno-geographic variation in internal exposure to OCPs, which likely reflects differences in consumption patterns. The inverse relationship observed between mirex concentration and markers of PCa aggressiveness need to be further investigated.

Investigating the Relationship Between Pollutant Concentrations in Human Pancreas and Adipose Tissues and Beta-cell Dysfunction

Epidemiological studies consistently report an association between circulating concentrations of persistent organic pollutants and increased diabetes risk in humans. We hypothesize that lipophilic pollutants accumulate in human pancreas tissue and cause beta-cell injury. To test this hypothesis, we measured the concentration of persistent pollutants from 3 chemical classes (dioxins, polychlorinated biphenyls [PCBs] and organochlorine pesticides [OCPs]) in pancreas and adipose tissues from 30 organ donors using GC-MS/MS.

Abstract P003: Chemerin Supports Basal Blood Pressure In Both Male And Female Dahl SS Rats

Evidence supports that Antisense oligonucleotides (ASO) against the adipokine chemerin reduce the blood pressure of the normal male Sprague Dawley rat and, to a greater magnitude, the hypertensive Dahl SS rat fed a high fat diet. In the Dahl SS rat, chemerin protein concentration in white adipose tissue [mesenteric perivascular adipose tissue (Mes PVAT)] was significantly higher in females vs males. We hypothesized that female Dahl SS rats would be more dependent on chemerin for blood pressure maintenance than males because of the Mes PVAT’s proximity to blood vessels that control total peripheral resistance. Age-matched male and female Dahl SS rats on a standard chow (0.2% NaCl, 6.2% fat) diet were used. Radiotelemeters were implanted to measure blood pressure (MAP) and heart rate (bpm). Following a two-week recovery period after implantation, one week of baseline measures were collected. Knockdown of whole body chemerin was achieved by subcutaneous injections of scrambled control ASO or whole-body ASO against chemerin (both 25 mg/kg) on days 0, 7, 14, and 21. On day 23, the rats were euthanized, and samples were collected for western blot and qPCR of the chemerin gene Rarres2 . Plasma chemerin was abolished in both male and female rats given the ASO against chemerin vs that of rats receiving the control ASO. In males and females, respectively, chemerin mRNA expression (2 -ΔCT ) was reduced from 0.53 to 0.001 ± 0.002 and 0.23 to 0.001 ± 0.02 in liver, 0.05 to 0.01 ± 0.005 and 0.07 to 0.005 ± 0.02 in RP fat, and 0.09 to 0.01 ± 0.003 and 0.05 to 0.001 ± 0.02 in epididymal/uterine fat. MAP in control ASO rats showed no significant change from baseline measurements (M:137.4 ± 3.0 /F: 130.6 ± 1.5 mmHg), while males and females treated with whole-body ASO dropped by 10.7 ± 1.6 and 10.9 ± 2.1 mmHg respectively after four injections, with no significant change in heart rate. Pulse pressure also decreased by 5.6 ± 1.3 and 6.8 ± 1.3 mmHg in whole-body ASO males and females, respectively, with no significant changes from baseline in the control animals. These data suggest, contrary to our hypothesis, that chemerin plays a similar role in basal blood pressure regulation in males and females. This indicates that males and females may be equally dependent on chemerin for high fat diet-induced hypertension.