Adipose Tissue Concentrations Research Articles

13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study

Despite the growing awareness regarding lutein's putative roles in eyes and brain, its pharmacokinetics and tissue distribution in primates have been poorly understood. We hypothesized that 13C-lutein will be differentially distributed into tissues of an adult rhesus macaque (Macaca mulatta) 3 days following a single oral dose. After a year of prefeeding a diet supplemented with unlabeled lutein (1 μmol/kg/d), a 19-year-old female was dosed with 1.92 mg of highly enriched 13C-lutein. Tissues of a nondosed, lutein-fed monkey were used as a reference for natural abundance of 13C-lutein. On the third day postdose, plasma and multiple tissues were collected. Lutein was quantified by high-performance liquid chromatography–photodiode array detector, and 13C-lutein tissue enrichment was determined by liquid chromatography quadrupole time-of-flight mass spectrometry. In the tissues of a reference monkey, 12C-lutein with natural abundance of 13C-lutein was detectable. In the dosed monkey, highly enriched 13C-lutein was observed in all analyzed tissues except for the macular and peripheral retina, with the highest concentrations in the liver followed by the adrenal gland and plasma. 13C-lutein accumulated differentially across 6 brain regions. In adipose depots, 13C-lutein was observed, with the highest concentrations in the axillary brown adipose tissues. In summary, we evaluated 13C-lutein tissue distribution in a nonhuman primate following a single dose of isotopically labeled lutein. These results show that tissue distribution 3 days following a dose of lutein varied substantially dependent on tissue type.

The mechanism through which dietary supplementation with heated linseed grain increases n-3 long-chain polyunsaturated fatty acid concentration in subcutaneous adipose tissue of cashmere kids.

The aim of this study was to investigate the effects of dietary supplementation with heated linseed on the fatty acid (FA) composition of the plasma, liver, and subcutaneous adipose tissue (SADT) of Albas white cashmere kids, particularly the effect on n-3 long-chain polyunsaturated FA profiles and the mRNA expression of genes related to lipid metabolism in SADT. Sixty 4-month-old castrated male kids (average BW 18.6 ± 0.1 kg) were selected and randomly allocated into three groups in a randomized block design. Three dietary treatments were used: (1) basal diet without supplementation (Control), (2) basal diet supplemented with linseed oil (LSO), and (3) basal diet supplemented with heated linseed grain (HLS). The diets were fed for 104 d, consisting of 14 d for adaptation followed by 90 d of measurement. Different FA profiles were found in SADT between LSO and HLS. Kids fed HLS had more C18:3n3 (P < 0.0001), C22:6n3 (P = 0.007), and n-3 PUFA (P < 0.0001) and a less (P < 0.0001) n-6/n-3 ratio than LSO kids. These FA differences between LSO and HLS kids were due to the increased expression of elongation of very long chain FA protein 5 (P < 0.0001), delta-6 desaturase (P < 0.0001), and peroxisome proliferator-activated receptor α (P = 0.003) in SADT of HLS kids and was also associated with liver fat metabolism. Together, these results suggest that the consumption of HLS leads to more C22:6n3 than LSO in SADT by increasing liver C22:6n3 content and by increasing SADT mRNA expression of ELOVL5 and FADS2 through promoting PPARα expression.

Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis

The intake of omega-6 vegetable oils, particularly soybean oil, began to increase in the USA starting in the early 1900s at a time when the consumption of butter and lard...

Virgin coconut oil is effective to treat metabolic and inflammatory dysfunction induced by high refined carbohydrate-containing diet in mice

The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.

Vancomycin concentrations in the cervical spine after intravenous administration: results from an experimental pig study

Background and purpose — Vancomycin may be an important drug for intravenous perioperative antimicrobial prophylaxis in spine surgery. We assessed single-dose vancomycin intervertebral disc, vertebral cancellous bone, and subcutaneous adipose tissue concentrations using microdialysis in a pig model.Material and methods — 8 female pigs received 1,000 mg of vancomycin intravenously as a single dose over 100 minutes. Microdialysis probes were placed in the C3–C4 intervertebral disc, C3 vertebral cancellous bone, and subcutaneous adipose tissue, and vancomycin concentrations were obtained over 8 hours. Venous blood samples were obtained as reference.Results — Ranging from 0.24 to 0.60, vancomycin tissue penetration, expressed as the ratio of tissue to plasma area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments. The lowest penetration was found in the intervertebral disc. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 4 µg/mL was 3, 17, 25, and 156 min for plasma, subcutaneous adipose tissue, vertebral cancellous bone, and the intervertebral disc, respectively. In contrast to the other compartments, a mean MIC of 8 µg/mL was not reached in the intervertebral disc. An approximately 3-times longer elimination rate was observed in the intervertebral disc in comparison with all the other compartments (p < 0.001), and the time to peak drug concentration was higher for all tissues compared with plasmaInterpretation — Preoperative administration of 1,000 mg of vancomycin may provide adequate vancomycin tissue concentrations with a considerable delay, though tissue penetration was incomplete. However, in order also to achieve adequate intervertebral disc concentrations in all individuals and accommodating a potentially higher MIC target, supplemental application of vancomycin may be necessary.

Melatonin increases magnesium concentrations in white adipose tissue and pancreas of diabetic obese rats

Melatonin is a natural bioactive compound, whose intake by obese diabetic Zucker (ZDF) rats improves this pathology. Hypomagnesaemia has also been observed in diabetes, and magnesium (Mg) is known to play an essential role in carbohydrate metabolism. In this study we have determined the effect of melatonin intake on Mg concentrations in white adipose tissues and organs in ZDF rats. This study reveals for the first time that melatonin intake increases Mg concentrations in subcutaneous lumbar, visceral, omentum, and gonadal adipose tissue and in the pancreas. These findings may be related to an improvement in the homeostatic regulation of adipocytokines produced by white adipose tissues, and to a reduction in plasmatic oxidative stress, which would lead to a decrease in insulin resistance and improvement in glucose homeostasis. These results open up the beneficial use of melatonin for the development of functional foods to ameliorate glucose homeostasis in obesity-associated diabetes.

Environmental phenols and parabens in adipose tissue from hospitalized adults in Southern Spain

Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain).Concentrations of bisphenol-A (BPA), benzophenone-3 (BP-3), triclosan (TCS), three chlorophenols (2,4-DCP, 2,5-DCP and 2,4,5-TCP) and two phenylphenols (2-PP and 4-PP), triclocarban (TCCB) and parabens [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP and i-PrP), butyl- (n-BuP and i-BuP) and benzyl-paraben (BzP)] were analysed in adipose tissue samples from a subcohort of 144 participants. Spearman correlation tests were performed, followed by stepwise multivariable linear regression analyses to assess determinants of the exposure.Detection frequencies and median concentrations were: BPA (86.8%, 0.54 ng/g tissue), BP-3 (79.2%, 0.60 ng/g tissue), TCS (45.8%, <LOD), 2-PP (18.8%, <LOD), MeP (100.0%, 0.40 ng/g tissue), EtP (20.1%, <LOD) and n-PrP (54.2%, 0.06 ng/g tissue). The remaining npEPs were detected in <10% of the samples. BPA, MeP, EtP and n-PrP levels were significantly and positively correlated, while BP-3 showed a positive correlation with TCS and 2-PP. Older participants showed higher concentrations of TCS and MeP, while BMI was inversely associated with most of the analysed compounds and perceived recent weight loss was inversely associated with 2-PP. Female participants and residents of rural areas had increased BP-3 concentrations. npEP concentrations were positively associated with the consumption of fatty food but negatively associated with the consumption of vegetables and fruit.This study reveals the widespread presence of numerous npEPs in adipose tissue from adults in southern Spain, suggesting a generalized distribution of these environmental compounds in fatty tissues. In these adults, many of the determinants of npEP concentrations in adipose tissue were similar to those of more lipophilic and persistent compounds.

The Relationship of Fasting Free Fatty Acids, Adipose Tissue, Insulin Resistance, and Fasting Glucose Concentrations with Subsequent ß-Cell Function in Nondiabetic Subjects

Elevations in both plasma free fatty acids (FFA) and glucose concentrations during fasting are associated with impaired β-cell function and predict progression from prediabetes to diabetes. Their interaction and subsequent effect on β-cell function as quantified by Disposition Index (DI) is unknown. We therefore measured total, saturated, mono-unsaturated and poly-unsaturated FFA concentrations using LC/MS in 120 nondiabetic subjects (across a range of fasting glucose &amp;lt; 6.9 mmol/l) who underwent a 2 hour oral glucose tolerance test (OGTT). Insulin secretion and action were quantified using the oral minimal model. The adipose tissue insulin resistance index (Adipo-IR) was calculated for each subject. Subjects were categorized by normal (NFG) or impaired (IFG) fasting glucose and by 2-hour glucose into normal (NGT) or impaired (IGT) glucose tolerance. Fasting total FFA were increased (p &amp;lt; 0.01) in IFG/IGT (835 ± 47 μmol/L) and in NFG/IGT (835 ± 30 μmol/L) but, intriguingly, not in IFG/NGT (593 ± 26 μmol/L) when compared to NFG/NGT (652 ± 29 μmol/L). These differences were no longer apparent within 60 minutes of OGTT and all groups suppressed FFA to the same nadir (166 ± 12 vs. 191 ± 18 vs. 184 ± 12 vs. 174 ± 17μmol/L, p = 0.59). On the other hand, an inverse relationship (p &amp;lt; 0.01) of fasting FFA (r = -0.33) and of Adipo-IR (r = -0.28) was observed with insulin action (Si). Fasting FFA did not correlate with β-cell responsivity (ϕ, r = 0.04). However, higher Adipo-IR was associated with higher values of ϕ (r = 0.36, p &amp;lt; 0.01). Fasting glucose concentrations did not alter these relationships; specifically no interaction of glucose with FFA during the fasting state to influence DI was evident. It remains to be ascertained whether the elevation in FFA reflects defects in production or in uptake, and whether the effect of changes in fasting glucose concentrations on DI is modulated by fasting FFA concentrations. Disclosure M.D. Hurtado: None. J. Adams: None. M.C. Laurenti: Other Relationship; Self; GlySens Incorporated. C. Dalla Man: None. C. Cobelli: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Novo Nordisk Inc.. R.A. Rizza: None. M.D. Jensen: Other Relationship; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. A. Vella: Research Support; Self; Novo Nordisk Inc., XOMA Corporation. Advisory Panel; Self; VTV Therapeutics, Bayer AG.

Hyperadiponectinemia During Infliximab Induction Therapy in Pediatric Crohn Disease.

The inflammatory process in Crohn disease (CD) involves the visceral fat, characterized by adipocyte hyperplasia and altered adipose tissue and serum concentrations of tumor necrosis factor (TNF), leptin, adiponectin and resistin. We investigated the effect of anti-TNF therapy with infliximab (IFX) on serum adipokine levels in pediatric CD. Serum concentrations of resistin (ng/mL), leptin (ng/mL), and total adiponectin (μg/mL) were assessed by enzyme-linked immunosorbent assays (ELISA) in 18 pediatric CD patients (mean age 15.0 ± 1.5 years) before first, second, and fourth IFX infusion (weeks 0, 2, and 14) and compared with baseline values from sex- and BMI-matched healthy controls (HC, mean age 13.4 ± 1.6 years). At baseline, CD patients (mean age 15.0 ± 1.5 years, 10 of 18 boys) compared with HC (13.4 ± 1.6 years, 7 of 15 boys) had higher resistin levels (median 14.7 ng/mL, range 5.1-50.5 vs 7.3 ng/mL, 0.5-14.5); P = 0.0002). At weeks 2 and 14, resistin decreased to 6.9 ng/mL (2.9-16.8) (P < 0.0001) and 9.2 ng/mL (4.1-20.6; P = 0.0011), respectively. Leptin and adiponectin were comparable between patients and HC at baseline. Leptin increased in girls from 9.5 ng/mL (4.0-30.1) to 16.0 ng/mL (7.9-35.2; P = 0.0156) and 17.2 ng/mL (10.8- 26.8; P = 0.1953) at weeks 0, 2, and 14 respectively; with a trend in boys from 2 (0.6-12.9) to 2.8 (1.7-8.6; P = 0.0840) and 3.3 (1.3-4.6; P = 0.1309). Adiponectin peaked initially from 7.8 μg/mL (4.6-11.9) at week 0 to 9.2 μg/mL (4.1-20.7; P = 0.0005) at week 2 and thereafter fell to 6.5 μg/mL (3.0-12.7; P = 0.0182) at week 14. TNF blockade is associated with changes in circulating adipokines. The marked early increase of the potent anti-inflammatory adiponectin may contribute to the rapid response to IFX in CD.

Les protéines purifiées à partir de sardines améliorent les chiffres tensionnels, l’équilibre glycémique, les voies métaboliques anti-athérogènes et la capacité anti-oxydante, chez le rat obèse

Aim of the studyThe effects of sardine by-products (SBy-P) and fillet proteins (SF-P) were compared to casein (Cas) ; these effects were assessed on blood pressure, glycemic control, reverse cholesterol transport, lipid peroxidation and total antioxidant capacity in obese rats. Materials and methodsEighteen male Wistar rats were subjected for three months, to a high-fat diet. The obese rats were divided into three groups and consumed the same high-fat diet for 28 days after addition of either, 20% SBy-P, SF-P or Cas. ResultsThe sardine proteins (SBy-P and SF-P) compared respectively to Cas, reduced diastolic (−14%, −11% P<0.05) and systolic pressures (−12%, −8% P<0.05), blood glucose (−24%, −21% P<0.05), glycated hemoglobin (−28%, −21% P<0.05), insulinemia (−29%, −18% P<0.05) and HOMA-IR index (−29%, −18% P<0.05). They improve the reverse cholesterol transport by increasing the lecithin: cholesterol acyltransferase (LCAT) activity (+43%, +30% P<0.05) and high-density lipoproteins in cholesterol esters (+108%, +88% P<0.05), and decreasing the atherogenicity ratios and membrane fluidity (P<0.05). Furthermore, SBy-P and SF-P induced a reduction of reactive thiobarbituric acid substances concentrations in heart (−45%, −25% P<0.05), aorta (−62%, −41% P<0.05), liver (−40%, −21% P<0.05) and adipose tissue (−50%, −37% P<0.05) with an improvement in antioxidant capacity. ConclusionSardine proteins, in particular those extracted from by-products, because of their hypotensive, hypoglycemic, anti-atherogenic and antioxidant properties, may have protective effects against the cardiovascular risk associated with obesity.

The Concentration of Iodine in Perigastric Adipose Tissue: A Novel Index for the Assessment of Serosal Invasion in Patients with Gastric Cancer after Neoadjuvant Chemotherapy

Objective: This study aims to explore the association between iodine concentration (IC) in perigastric adipose tissue (PAT), quantified by dual-energy computed tomography (DECT) and serosal invasion (SI) in patients with gastric cancer post-neoadjuvant chemotherapy (NAC). Methods: Forty-three patients with T4-staged gastric cancer were enrolled. IC and standardized IC in PAT (IC_PAT and SIC_PAT) were quantified by DECT pre and post NAC. A postoperative pathologic examination was performed to stage gastric cancer. Results: After NAC, a total of 43 participants were assigned to group A with 13 patients and group B with 30 patients according to the results of the postoperative pathologic examination. The accuracy of conventional CT in identifying SI was 74.42%. Differences of variations between pre- and post- NAC IC_PAT, SIC_PAT, ∆IC_PAT, and ∆SIC_PAT were observed respectively (p < 0.05). Intragroup IC_PAT and SIC_PAT also changed significantly after NAC (p < 0.05). The area under the ROC curve was 0.929, with the threshold of ∆SIC_PAT reaching 0.095. The sensitivity, specificity, and accuracy of SIC_PAT in identifying post-NAC SI were 92.30, 86.70, and 88.37% respectively. Moreover, the 2 measurements in the same patient maintain a high level of consistency. Conclusion: These results showed that SIC_PAT is a reliable index for identifying post-NAC SI.

Evaluation of alkylresorcinols in adipose tissue biopsies as a long-term biomarker of whole-grain wheat and rye intake in free-living Swedish men and women.

Wheat and rye, the most consumed whole grains (WG) in the Nordic countries, contain alkylresorcinols (AR) in their bran. AR concentrations in human adipose tissue might reflect long-term WG rye and wheat intake. We aimed to evaluate AR concentrations in adipose tissue biopsies as a long-term biomarker of WG wheat and rye intake in free-living Swedish men and women. Cross-sectional study. AR concentrations in adipose tissue biopsies were analysed and compared with long-term WG intake assessed by three FFQ (repeated over a period of 14 years in men, 17 years in women) and with plasma AR concentrations. The Cohort of Swedish Men between 1997 and 2010 and the Swedish Mammography Cohort between 1987 and 2003, Sweden. Men (n 149) and women (n 109). Long-term WG rye intake estimated with repeated FFQ correlated (r=0·31-0·41, P<0·01) with adipose-tissue AR concentrations, while WG wheat intake correlated only weakly (r=0·17-0·33, P<0·05). Total AR concentration in adipose tissue was 61 % lower in women than in men at similar energy-adjusted WG wheat and rye intakes, but plasma concentrations were similar. AR concentrations in adipose tissue correlated well with plasma concentrations (r=0·49-0·81, P<0·001). AR in adipose tissue reflected long-term WG rye but not WG wheat intake, probably due to poor precision in estimating WG wheat intake by FFQ. AR in adipose tissue appears promising as a biomarker of long-term WG rye intake but should be adjusted for sex.

Persistent organic pollutants and penile bone mineral density in East Greenland and Canadian polar bears (Ursus maritimus) during 1996–2015

Persistent organic pollutants (POPs) are long-range transported to the Arctic via atmospheric and oceanic currents, where they biomagnify to high concentrations in the tissues of apex predators such as polar bears (Ursus maritimus). A major concern of POP exposure is their physiological effects on vital organ-tissues posing a threat to the health and survival of polar bears. Here we examined the relationship between selected POPs and baculum bone mineral density (BMD) in the East Greenland and seven Canadian subpopulations of polar bears. BMD was examined in 471 bacula collected between years 1996–2015 while POP concentrations in adipose tissue were determined in 67–192 of these individuals collected from 1999 to -2015. A geographical comparison showed that baculum BMD was significantly lowest in polar bears from East Greenland (EG) when compared to Gulf of Boothia (GB), Southern Hudson (SH) and Western Hudson (WH) Bay subpopulations (all p < 0.05). The calculation of a T-score osteoporosis index for the EG subpopulation using WH bears as a reference group gave a T-score of −1.44 which indicate risk of osteopenia. Concentrations of ΣPCB74 (polychlorinated biphenyls), ΣDDT3 (dichlorodiphenyltrichloroethanes), p,p′-DDE (dichlorodiphenyldichloroethylene), ΣHCH3 (hexachlorohexane) and α-HCH was significantly highest in EG bears while ΣPBDE (polybrominated diphenyl ethers), BDE-47 and BDE-153 was significantly highest in SH bears (all p < 0.04). Statistical analyses of individual baculum BMD vs. POP concentrations showed that BMD was positively correlated with ΣPCB74, CB-153, HCB (hexachlorobenzene), ΣHCH, β-HCH, ClBz (chlorobenzene), ΣPBDE and BDE-153 (all p < 0.03). In conclusion, baculum density was significantly lowest in East Greenland polar bears despite the positive statistical correlations of BMD vs. POPs. Other important factors such as nutritional status, body mass and body condition was not available for the statistical modelling. Since on-going environmental changes are known to affect these, future studies need to incorporate nutritional, endocrine and genetic parameters to further understand how POP exposure may disrupt bone homeostasis and affect baculum BMD across polar bear subpopulations.

Organochlorine concentrations in adipose tissue and survival in postmenopausal, Danish breast cancer patients

BackgroundSeveral studies have investigated an association between organochlorine-concentrations and breast cancer incidence, whereas few have investigated an association with breast cancer mortality. MethodsWe used Cox Proportional Hazards Models to estimate the association between adipose organochlorine-concentrations and mortality after breast cancer in a survivor-cohort of 399 postmenopausal women. During a median follow-up of 16.1 years, 177 women died; 119 from breast cancer. ResultsThere was a general inverse association with PCB-concentration (e.g. ΣPCBs: Mortality Rate Ratio (MRR) 0.79, 95% confidence interval (CI) (0.64–0.98) per inter-quartile range (IQR)), and for all pesticides, except β-Hexachlorocyclohexane, which was not associated with mortality (MRR 1.02(0.87–1.18) per IQR), and dieldrin, which was associated with a significantly increased risk of death (MRR 1.22(1.05–1.41) per IQR). We found an interaction with prognostic factors for all PCBs, confining the inverse association to those with adverse prognostic factors. Results for pesticides suggested a similar, but mostly non-significant interaction. Dieldrin diverged from the general picture by being associated with increased mortality across all strata. ConclusionA higher concentration of PCBs and several organochlorine pesticides may be inversely associated with breast cancer mortality among women with adverse prognostic factors. Further studies are required to investigate if this is a causal association. Dieldrin was associated with a higher mortality, regardless of prognostic factors. ImpactThis is the first study to investigate an association between organochlorine concentrations in adipose tissue and breast cancer mortality. A prominent finding is a strong interaction with prognostic factors. The unexpected direction of association for most organochlorines encourages further studies of the role of individual metabolism of the organochlorines and a potentially stronger effect of the metabolites on mortality.

No Association between Organochlorine Concentrations in Adipose Tissue and Survival after Non-Hodgkin Lymphoma.

Background: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the world. Involvement of organochlorines has been proposed in disease etiology. No study has investigated organochlorine exposure in relation to survival after a NHL diagnosis.Methods: In a survivor cohort consisting of 232 NHL cases from the Danish Diet, Cancer and Health cohort, we examined the association between adipose tissue organochlorine concentrations [polychlorinated biphenyls (PCBs) and pesticides] and subsequent survival, using Cox proportional hazards models.Results: We found no statistically significant association between organochlorine concentrations and subsequent survival. If anything, there was a nonsignificant tendency toward an inverse association with PCBs, but not pesticides.Conclusions: In conclusion, the current study does not support an increased risk of death among NHL patients with high tissue concentrations of organochlorines.Impact: This is the first study to investigate adipose organochlorine concentrations and survival after a NHL diagnosis. Cancer Epidemiol Biomarkers Prev; 27(2); 224-6. ©2017 AACR.

Organophosphate esters in East Greenland polar bears and ringed seals: Adipose tissue concentrations and in vitro depletion and metabolite formation

East Greenland is a contamination “hot spot” for long-range transported anthropogenic chemicals, including organophosphate esters (OPEs). High concentrations of OPEs have been reported in arctic air while very little is known for wildlife where OPE tissue residues levels appear to be strongly influenced by biotransformation. In the present study, the hepatic in vitro metabolism of six environmentally relevant organophosphate (OP) triesters and corresponding OP diester formation were investigated in East Greenland polar bears (PBs) and ringed seals (RSs). The in vitro metabolism assay results were compared to adipose levels in field samples from the same individuals. In vitro OP triester metabolism was generally rapid and structure-dependent, where PBs metabolized OPEs more rapidly than RSs. Exceptions were the lack of triethyl phosphate (TEP) metabolism and slow metabolism of tris(2-ethylhexyl) phosphate (TEHP) in both species. OP diester metabolites were also formed with the exception of TEP which was not metabolized at all. Tris(1,3-dichloro-2-propyl) phosphate was completely converted to its corresponding diester. However, the mass balances showed that OP diester formation corresponding to TEHP, tri(n-butyl) phosphate, and tris(2-butyoxyethyl) phosphate did not account for 100% of the OP triester depletion, which indicated alternate pathways of OP triester metabolism had occurred. Triphenyl phosphate was completely converted to its OP diester metabolite in PBs but not in RSs suggesting species-specific differences. The results demonstrated that OP triester bioaccumulation and fate in PBs versus their RS prey is substantially influenced by biotransformation.

Raldh1 promotes adiposity during adolescence independently of retinal signaling.

All-trans-retinoic acid (RA) inhibits adipogenesis in established preadipocyte cell lines. Dosing pharmacological amounts of RA reduces weight gain in mice fed a high-fat diet, i.e. counteracts diet-induced obesity (DIO). The aldehyde dehydrogenase Raldh1 (Aldh1a1) functions as one of three enzymes that converts the retinol metabolite retinal into RA, and one of many proteins that contribute to RA homeostasis. Female Raldh1-ablated mice resist DIO. This phenotype contrasts with ablations of other enzymes and binding-proteins that maintain RA homeostasis, which gain adiposity. The phenotype observed prompted the conclusion that loss of Raldh1 causes an increase in adipose tissue retinal, and therefore, retinal functions independently of RA to prevent DIO. A second deduction proposed that low nM concentrations of RA stimulate adipogenesis, in contrast to higher concentrations. Using peer-reviewed LC/MS/MS assays developed and validated for quantifying tissue RA and retinal, we show that endogenous retinal and RA concentrations in adipose tissues from Raldh1-null mice do not correlate with the phenotype. Moreover, male Raldh1-null mice resist weight gain regardless of dietary fat content. Resistance to weight gain occurs during adolescence in both sexes. We show that RA concentrations as low as 1 nM, i.e. in the sub-physiological range, impair adipogenesis of embryonic fibroblasts from wild-type mice. Embryonic fibroblasts from Raldh1-null mice resist differentiating into adipocytes, but retain ability to generate RA. These fibroblasts remain sensitive to an RA receptor pan-agonist, and are not affected by an RA receptor pan-antagonist. Thus, the data do not support the hypothesis that retinal itself represses weight gain and adipogenesis independently of RA. Instead, the data indicate that Raldh1 functions as a retinal and atRA-independent promoter of adiposity during adolescence, and enhances adiposity through pre-adipocyte cell autonomous actions.

Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients

Background and purpose — The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin using microdialysis in male patients undergoing total knee replacement.Methods — 1,000 mg of vancomycin was administered postoperatively intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, SCT, cancellous, and cortical bone were measured over the following 8 hours. Microdialysis was applied for sampling in solid tissues.Results — For all solid tissues, tissue penetration of vancomycin was significantly impaired. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2 mg/L was 3, 36, 27, and 110 min for plasma, SCT, cancellous, and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4 mg/L could not be reached in cortical bone. The area under the concentration-time curve from 0 to the last measured value and peak drug concentrations (Cmax) for SCT, cancellous, and cortical bone was lower than that of free plasma. The time to Cmax was higher for all tissues compared with free plasma.Interpretation — Postoperative penetration of vancomycin to bone and SCT was impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached using standard prophylactic dosage.

COMPARISON OF ORGANOCHLORINE PESTICIDE LEVELS BETWEEN HUMAN BLOOD SERUM AND ADIPOSE TISSUE

The organochlorine pesticides, being lipophilic compounds, show extremely high thermodynamic stability and resistance to degradation processes in the environment and in living organisms. They accumulate in lipid rich tissues and distribute between transport compartment (blood) and store compartment (adipose tissue). The purpose of this study is to make a comparison between organochlorine pesticide levels in blood serum and adipose tissue and calculate the differences in their concentrations based on routine biomonitoring study. One hundred and twenty six pair samples of adipose tissue and blood serum during autopsies as a case study were taken and analyzed in Los Mochis Sinaloa, Mexico. Among organochlorine pesticides, higher concentrations correspond to b-HCH, pp’DDE and op’DDT in blood serum lipids; and pp’DDT shows higher concentrations in adipose tissue. Using statistical comparisons, we found a significant linear association of lipid serum organochlorine pesticide concentrations with that in adipose tissue. This concludes that serum lipid organochlorine pesticide concentrations represent an important indicator for both human biological matrices.

Activated carbon, a useful medium to bind chlordecone in soil and limit its transfer to growing goat kids.

Chlordecone (Kepone) (CLD) is a highly persistent pesticide which was extensively used in the French West Indies; high levels of CLD can still currently be found in large agricultural areas. As CLD transfers from soil to animals mainly via involuntary ingestion, the consumption of foodstuffs derived from animals raised in contaminated areas may significantly contribute to exposure of humans to CLD. The present study was designed to test the efficacy of two different activated carbons (ACs) sources in limiting CLD transfer from soil to animal. Three soils (ASs) were prepared according to the OECD guideline 207. One standard soil (SS) lacking AC, and two modified preparations of SS supplemented with 2% coconut-based activated carbon (ORBO), SSO or with 2% lignite-based one (DARCO), SSD. All three soils were spiked with 10 μg of kepone per g of dry matter and aged for three weeks. This study involved 15 goat kids randomly assigned to the 3 experimental groups (n = 5/group), which were fed the experimental matrices at an exposure dose of 10 μg CLD per kg of body weight per day. After 21 d of oral exposure, CLD in adipose tissue and liver were analysed by LC-MS-MS. A significant decrease of 63.7% and 74.7% of CLD concentrations in adipose tissue and liver, respectively, were obtained from animals exposed using SS containing DARCO as compared to those receiving only SS. Decreases in CLD levels of 98.2% (adipose tissue) and 98.7% (liver) were obtained for animals exposed using SS containing ORBO. This study leads us to conclude that (i) the presence of AC in CLD-contaminated soil strongly reduces CLD bioavailability, and (ii) the efficacy depends on the nature and characteristics of the AC used.