Adipose Tissue Concentrations Research Articles

Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice.

Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12weeks (body weight: KO 34.6 ± 5.6g vs WT 40.1 ± 5.2g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes.

Adipose tissue concentrations of arsenic, nickel, lead, tin, and titanium in adults from GraMo cohort in Southern Spain: An exploratory study

BackgroundAdipose tissue has been acknowledged as a potential target for obesogenic pollutants, including toxic metal(loid)s. However, the presence of these chemicals in the adipose tissue has been poorly characterized. ObjectiveTo examine the distributions of adipose tissue concentrations of five toxic metal(loid)s (i.e., arsenic [As], nickel [Ni], lead [Pb], tin [Sn], and titanium [Ti]) in adults, and potential socio-demographic and lifestyle factors associated with metal(loid) concentrations. MethodsThe study population consisted of a subsample of 228 subjects from GraMo cohort in Southern Spain (N = 387). Adipose tissue samples were intra-operatively collected from adults recruited in 2003–2004 in two public hospitals, and concentrations of metal(loid)s in adipose tissue were analyzed in 2015 by High-Resolution Inductively Coupled Plasma Mass Spectrometry. Data on socio-demographic and lifestyle factors were obtained by baseline questionnaire completion. Linear and multinomial regression was used to identify factors associated with metal(loid) levels. ResultsNi, Pb, Sn, and Ti were detected in all adipose tissue samples, and As in 51% of them. Ni was the metal showing the highest median concentration (0.56 μg/g), followed by Ti (0.31 μg/g), Pb (0.08 μg/g), Sn (0.06 μg/g), and As (0.003 μg/g). Predictors of As levels included area of residence, social class, and oily fish intake; for Ni: area of residence and consumption of cheese, meat, eggs, and canned food; for Pb: vegetables intake and industrial occupation; for Sn: age, body mass index, and consumption of lean fish, eggs, and milk; and cheese intake for Ti. Some of these predictors were sex-specific, particularly those regarding dietary intake. ConclusionsThis exploratory study provides the first evidence of the occurrence of Ni, Pb, Sn, Ti, and As in adipose tissue from adult population, and highlights the potential of this tissue as a biological matrix for studying exposure levels and chronic health effects of toxic metal(loid)s.

Chlorinated Paraffins in Two Snake Species from the Yangtze River Delta: Tissue Distribution and Biomagnification

Very-short, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in different tissues of the terrestrial short-tailed mamushi (Gloydius brevicaudus) and the semi-aquatic red-backed rat snake (Elaphe rufodorsata) from the Yangtze River Delta, China. The total CP concentrations in liver, muscle, and adipose tissues in the two snake species were in the range of 2500-24 000, 4900-48 000, and 12-630 ng/g lw, respectively. Tissue burdens indicated that vSCCPs (C6-9) and SCCPs (C10-13) preferentially distributed to snake liver, while adipose was an important storage site and sink of MCCPs (C14-17) and LCCPs (C>18). On a lipid weight basis, vSCCPs and SCCPs were found in highest concentrations in red-backed rat snake liver and MCCPs and LCCPs in muscle, whereas for short-tailed mamushi, all CP groups were predominant in muscle, probably reflecting ecosystem/food web differences. Moreover, vSCCPs, SCCPs, MCCPs, and LCCPs were found to be biomagnified from black-spotted frogs to red-backed rat snakes with mean (maximum) biomagnification factors of 2.2 (3.4), 1.9 (3.7), 1.8 (2.8), and 1.7 (4.5), respectively. This is the first field study of biomagnification potential involving vSCCPs and LCCPs and highlights the need to include all CPs in studies.

Effects of Training and Octopamine Supplementation on Expression of M1 and M2 Monocyte/Macrophage Surface Markers in White Adipose Tissue of Rats Poisoned with Deep-Fried Oil

Background It showed that the infiltration of macrophages into adipose tissue is the origin of inflammation. Despite the positive effect of training and octopamine on the inflammatory process and adipose tissue permeability to macrophages, the simultaneous effect of aerobic training (AT) and octopamine (O), as a lipolytic agent on macrophage permeability in a high-fat diet situation, is unclear.Objectives This study aimed to investigate the effect of AT and O supplementation on CD86 and CD206 concentration in white adipose tissue of rats poisoned with deep-fried oil (DFO).Methods A total of 30 male Wistar rats were divided into groups, including healthy control, DFO control, AT + DFO, O + DFO, and AT + O + DFO. During the four weeks the O groups received 81 μmol/kg octopamine for five days/week intraperitoneally, and AT groups performed training with moderate intensity (26 m/min). Forty-eight hours after the last intervention, the rats were anesthetized and subcutaneous adipose tissue was removed for CD86 and CD206 assays.Results DFO significantly increased CD86 and reduced CD206; AT was able to reduce the CD86 increase, however, it had no effect on CD206; O significantly reduced CD86 and increased CD206; in addition, interaction of AT and O on CD86 was significant.Conclusions Both AT and O can reduce the negative effect of deep-fried oil on macrophage permeability in adipose tissue.

Obesity and Insulin Resistance Are Inversely Associated with Serum and Adipose Tissue Carotenoid Concentrations in Adults

Background:Low tissue concentrations of carotenoids have been suggested to contribute to insulin resistance in obesity. Objectives:The objectives of the study were to 1) evaluate the relations of adipose tissue and serum carotenoids with body fat, abdominal fat distribution, muscle, adipose tissue and liver insulin resistance, and dietary intake; 2) evaluate the relations and distributions of carotenoids detected in adipose tissue and serum; and 3) compare serum carotenoids and retinol concentrations in subjects with and without obesity. Methods:Post hoc analysis of serum and adipose tissue carotenoids in individuals [n = 80; 31 men, 49 women; age (mean ± SEM): 51.4 α 1.1 y] who participated in 2 separate studies conducted at the Clinical Research Facility at the Garvan Institute of Medical Research (Sydney) between 2008 and 2013. Retinol, α-carotene, β-carotene, ζ-carotene, lutein, lycopene, phytoene, and phytofluene were measured using HPLC. Body composition was measured by dual-energy X-ray absorptiometry. Insulin resistance was measured by 2-step hyperinsulinemic-euglycemic clamps with deuterated glucose (n = 64), and subcutaneous and visceral abdominal volume and liver and pancreatic fat by MRI (n = 60). Periumbilical subcutaneous fat biopsy was performed and carotenoids and retinol measured in the tissue (n = 16). Results:We found that ζ-carotene, phytoene, and phytofluene were stored in considerable amounts in adipose tissue (25% of adipose tissue carotenoids). Carotenoid concentrations in adipose tissue and serum correlated significantly, but they followed different distributions: ζ-carotene was 3-fold higher in adipose tissue compared with serum, while lutein and lycopene made up 20% and 21% of serum carotenoids compared with 2% and 12% of adipose tissue carotenoids, respectively. Liver (P ≤ 0.028) and adipose tissue (P = 0.023), but not muscle (P ≥ 0.16), insulin resistance correlated inversely with many of the serum carotenoids. Conclusions:Multiple serum and adipose tissue carotenoids are associated with favorable metabolic traits, including insulin sensitivity in liver and adipose tissue in humans.

Quantification of Fat Concentration and Vascular Response in Brown and White Adipose Tissue of Rats by Spectral CT Imaging.

ObjectiveThe purpose of the study was to non-invasively characterize and discriminate brown adipose tissue (BAT) from white adipose tissue (WAT) in rats using spectral computed tomography (CT) with histological validation.Materials and MethodsA lipid-containing phantom (lipid fractions from 0% to 100%) was imaged with spectral CT. An in vivo, non-enhanced spectral CT scan was performed on 24 rats, and fat concentrations of BAT and WAT were measured. The rats were randomized to receive intraperitoneal treatment with norepinephrine (NE) (n = 12) or saline (n = 12). Non-enhanced and enhanced spectral CT scans were performed after treatment to measure the elevation of iodine in BAT and WAT. The BAT/aorta and WAT/aorta ratios were calculated and compared, after which isolated BAT and WAT samples were subjected to histological and uncoupling protein 1 (UCP1) analyses.ResultsThe ex-vivo phantom study showed excellent linear fit between measured fat concentration and the known gravimetric reference standard (r2 = 0.996). In vivo, BAT had significantly lower fat concentration than WAT (p < 0.001). Compared to the saline group, the iodine concentration of BAT increased significantly (p < 0.001) after injection of NE, while the iodine concentration of WAT only changed slightly. The BAT/aorta ratio also increased significantly after exposure to NE compared to the saline group (p < 0.001). Histological and UCP1 expression analyses supported the spectral CT imaging results.ConclusionThe study consolidates spectral CT as a new approach for non-invasive imaging of BAT and WAT. Quantitative analyses of BAT and WAT by spectral CT revealed different characteristics and pharmacologic activations in the two types of adipose tissue.

Evaluation of two contrasted activated carbon-based sequestration strategies to reduce soil-bound chlordecone bioavailability in piglets.

Chlordecone (Kepone) (CLD) is a highly persistent pesticide formerly used in the French West Indies. High levels of this pesticide are still found in soils and represent a subsequent source of contamination for outdoor-reared animals which may ingest involuntary non negligible amounts of soil. In that context, sequestering matrices like activated carbons (ACs) may be used to efficiently decrease the bioavailability of such organic pollutants. The present study intends to assess the respective efficiency of two sequestering strategies where two different ACs were provided either via feed incorporation or via soil amendment. This study involved 20 piglets randomly distributed into 5 experimental groups (4 replicates). All groups were exposed to 10 μg of CLD per kg of BW per day during 10 days via a contaminated soil. In both "Soil-ACs" treatment groups, the contaminated soil was amended by 2% (mass basis) of one of the two ACs. The two "Feed-ACs" groups received the contaminated soil and one dough ball containing 0.5% (mass basis) of one of the ACs. The piglets were then euthanized before collection of pericaudal adipose tissue and the whole liver and CLD analysis. A significant decrease of CLD concentrations in liver and adipose tissue was observed only in the "Soil-ACs" groups in comparison with the control group (P < 0.001). This decrease was particularly important for the coconut shell activated carbon where relative bioavailability was found lower than 1.8% for both tissues.

Female Mice Exposed to Postnatal Neglect Display Angiotensin II-Dependent Obesity-Induced Hypertension.

BackgroundWe have previously reported that female mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show exacerbated diet‐induced obesity associated with hypertension. The goal of this study was to test whether MSEW promotes angiotensin II–dependent hypertension via activation of the renin‐angiotensin system in adipose tissue.Methods and ResultsMSEW was achieved by daily separations from the dam and weaning at postnatal day 17, while normally reared controls were weaned at postnatal day 21. Female controls and MSEW weanlings were placed on a low‐fat diet (LF, 10% kcal from fat) or high‐fat diet (HF, 60% kcal from fat) for 20 weeks. MSEW did not change mean arterial pressure in LF–fed mice but increased it in HF–fed mice compared with controls (P<0.05). In MSEW mice fed a HF, angiotensin II concentration in plasma and adipose tissue was elevated compared with controls (P<0.05). In addition, angiotensinogen concentration was increased solely in adipose tissue from MSEW mice (P<0.05), while angiotensin‐converting enzyme protein expression and activity were similar between groups. Chronic enalapril treatment (2.5 mg/kg per day, drinking water, 7 days) reduced mean arterial pressure in both groups of mice fed a HF (P<0.05) and abolished the differences due to MSEW. Acute angiotensin II–induced increases in mean arterial pressure (10 μg/kg SC) were attenuated in untreated MSEW HF–fed mice compared to controls (P<0.05); however, this response was similar between groups in enalapril‐treated mice.ConclusionsThe upregulation of angiotensinogen and angiotensin II in adipose tissue could be an important mechanism by which female MSEW mice fed a HF develop hypertension.

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level.

Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI 20–24.9 kg/m2) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P < 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, rs = −0.525), miR-125b-5p (P = 0.001, rs = −0.495), and miR-214-3p (P = 0.009, rs = −0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1β, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n = 144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders.Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(β) = 1.20, p = 0.060] and decreased levels of reduced glutathione (GSH) [exp(β) = 0.55, p = 0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(β) = 0.83, exp(β) = 0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(β) = 1.73, p-value = 0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79].Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.

Bile acid-polymer-probucol microparticles: protective effect on pancreatic β-cells and decrease in type 1 diabetes development in a murine model

Studies in our laboratory have shown potential applications of the anti-atherosclerotic drug probucol (PB) in diabetes due to anti-inflammatory and β-cell protective effects. The anti-inflammatory effects were optimized by incorporation of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA). This study aimed to test PB absorption, tissue accumulation profiles, effects on inflammation and type 1 diabetes prevention when combined with UDCA. Balb/c mice were divided into three equal groups and gavaged daily PB powder, PB microcapsules or PB-UDCA microcapsules for one week, at a constant dose. Mice were injected with a single dose of intraperitoneal/subcutaneous alloxan to induce type-1 diabetes and once diabetes was confirmed, treatments were continued for 3 days. Mice were euthanized and blood and tissues collected for analysis of PB and cytokine levels. The PB-UDCA group showed the highest PB concentrations in blood, gut, liver, spleen, brain, and white adipose tissues, with no significant increase in pancreas, heart, skeletal muscles, kidneys, urine or feces. Interferon gamma in plasma was significantly reduced by PB-UDCA suggesting potent anti-inflammatory effects. Blood glucose levels remained similar after treatments, while survival was highest among the PB-UDCA group. Our findings suggest that PB-UDCA resulted in best PB blood and tissue absorption and reduced inflammation.

Relationship of Total Hemoglobin in Subcutaneous Adipose Tissue with Whole-Body and Visceral Adiposity in Humans

High whole-body and visceral adiposity are risk factors that can cause metabolic diseases. We hypothesized that the total hemoglobin concentration (total-Hb) in abdominal subcutaneous adipose tissue (SATab), an indicator of white adipose tissue (WAT) vascularity, correlates negatively with risk factors for developing metabolic diseases, such as whole-body and visceral adiposity. We tested the optical characteristics of abdominal tissue in 140 participants (45 men and 95 women) who were apparently healthy individuals with a median age of 39 years. They also had a median body fat percentage of 25.4%, a visceral fat area of 50.4 cm2, and a SATab thickness of 1.05 cm. These tests were conducted using near-infrared time-resolved spectroscopy (NIRTRS) with a 2-cm optode separation. To distinguish the segments of SATab (SegSAT) and the mixture of muscle and SATab (SegSAT+Mus), the threshold was analyzed using the slopes of (total-Hb) against the thickness of SATab using the least-squares mean method. According to the results from the logistic regression analysis, the percentage of body fat and visceral fat area remained significant predictors of the (total-Hb) (p = 0.005 and p = 0.043, respectively) in the data for SegSAT (no influence from the SATab thickness). We conclude that simple, rapid, and noninvasive NIRTRS-determined (total-Hb) in WAT could be a useful parameter for evaluating risk factors for metabolic diseases.

Lack of Pharmacokinetic Basis of Weight-Based Dosing and Intra-Operative Re-Dosing with Cefazolin Surgical Prophylaxis in Obese Patients: Implications for Antibiotic Stewardship.

Traditionally, there have been uniform antibiotic dosing guidelines for prophylaxis for clean-clean-contaminated surgery in both non-obese and obese adults. All other factors predisposing to surgical site infections (SSIs) being equal, over time, the preferred drug is cefazolin. The usual dose, given immediately pre-procedure, has been 1 g intravenously (IV) in non-penicillin-allergic patients, which has been highly effective, Recently, it has become common practice to use high-dose cefazolin; i.e., 3 g IV, in obese patients. This article reviews the literature on high-dose cefazolin prophylactic regimens in the obese from a pharmacokinetic (PK) point of view. There are no comparative studies to support this approach, which is based largely on the theory "more must be better." Weight-based dosing of cefazolin in the obese is flawed, because it does not take into account PK factors, which are critical in the obese. Cefazolin is a water-soluble (hydrophilic) antibiotic that does not penetrate adipose tissue regardless of IV dose. Importantly, adipose tissue is not a valid target tissue in clean-clean-contaminated SSI prophylaxis, as it does not become infected. Higher doses result in proportionately higher serum/non-adipose tissue concentrations, but adipose tissue concentrations are unaffected. Cefazolin displays time-dependent killing kinetics so that as long as serum/tissue concentrations are above the minimum inhibitory concentration (MIC) of SSI pathogens, there is no enhanced killing with higher concentrations relative to concentration-dependent antibiotics. Taking into account PK principles, a cefazolin 1 g IV bolus results in peak serum concentrations of ∼185 mcg/mL, provides at least six hours of intra-operative protection, aside from any post-antibiotic effects, and eliminates any rationale for intra-operative re-dosing for procedures lasting six hours or less. Some have argued that a cefazolin 3 g IV dose in the obese does not matter, as more must necessarily be better. However, from an antibiotic stewardship program (ASP) perspective, unneeded antibiotics are unnecessary. Moreover, the costs of cefazolin 1 g (IV push) at $0.75 versus 2 g (IV piggyback) at $ 6.83 can be significant in large centers using cefazolin prophylaxis for cardiothoracic, orthopedic, obstetric/gynecology, and bariatric surgery. Excessive antibiotics also expose the patient to potential adverse effects; i.e., Clostridium difficile. There is no dose-dependent or duration of exposure effect on resistance with one or two pre-operative or intra-operative doses. Well-done PK-based studies in obese patients clearly demonstrate the lack of benefit of using a 3-g dose or intra-operative re-dosing and show no incremental increase in adipose tissue concentrations with high doses. From an ASP point of view, antibiotic dosing recommendations should be reviewed and revised on the basis of PK principles that indicate that weight-based dosing has no basis for pre-operative prophylaxis in obese patients.

Beneficial effects of non-quinazoline α1-adrenolytics on hypertension and altered metabolism in fructose-fed rats. A comparison with prazosin

Background and aimsMetabolic syndrome associated with insulin resistance and hypertension is often caused by excessive fructose consumption. Treatment of hypertension in patients with metabolic syndrome is a difficult task as many antihypertensive drugs have adverse effects on the metabolic profile. We investigated if MH-76 and MH-79, non-quinazoline α1-adrenoceptor antagonists with an additional ability to stimulate NO/cGMP/K+ pathway, ameliorates metabolic syndrome in fructose-fed rats. As reference compound prazosin was used. Methods and resultsMale rats were divided into 5 groups (n = 8) and studied for 18 weeks: group control: standard diet and drinking water; group Fructose: high-fructose diet (20% fructose in drinking water); groups Fructose + MH-76, Fructose + MH-79, Fructose + prazosin: high-fructose diet with subsequent MH-76, MH-79 (5 mg/kg/day ip) or prazosin (0.2 mg/kg/day ip) treatment 12 weeks later. In addition to their antihypertensive effect, the studied compounds reversed endothelial dysfunction, decreased hyperglycemia and hypertriglyceridemia, as well as prevented abdominal adiposity. Moreover, MH-76 reduced insulin resistance and decreased TNF-α concentration and lipid peroxidation in adipose tissue. Prazosin treatment exerted an antihypertensive effect, reduced hyperglycemia but did not improve endothelial dysfunction, insulin resistance, and abdominal adiposity. The lower efficacy of prazosin may be the result of its short half-time and the lack of described pleiotropic effects. Conclusionsα1–adrenoceptor blockade, endothelial protection, TNF-α suppressing and antioxidant activity together with favorable pharmacokinetic parameters determines high efficacy of MH-76, leading to the effective improvement of hemodynamic and metabolic disturbances in metabolic syndrome. The use of non-quinazoline, multiple-targeted α1-blockers may be an interesting option for treatment of hypertension with metabolic complications.

Levels and determinants of adipose tissue cadmium concentrations in an adult cohort from Southern Spain

This study was conceived as a first step to evaluate the suitability of adipose tissue cadmium (Cd) concentrations as a biomarker for the assessment of long-term exposure. Specifically, the aim of this work was to explore the socio-demographic, dietary, and lifestyle determinants of adipose tissue Cd concentrations.The study population is a subsample of GraMo cohort. Adipose tissue samples were intraoperatively collected from 226 adult volunteers recruited in two public hospitals from Granada, Spain. Cd concentrations in adipose tissue were analyzed by High-Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS). Data on socio-demographic characteristics, lifestyle, diet and health status were collected by face-to-face interviews. Predictors of Cd concentrations were assessed by multivariable linear regression with a stepwise variable selection.We found detectable levels of Cd in the adipose tissue of all the study participants, with a mean concentration (±standard deviation) of 12.66 ± 18.91 μg/kg. Smoking habit at recruitment was associated with increased adipose tissue Cd concentrations (β for smokers = 0.669 p < 0.001; β for former smokers = 0.502, p < 0.001; reference = non-smokers). Age was positively associated with Cd concentrations (β = 0.014, p < 0.001), and men showed lower concentrations than women (β = −0.424, p < 0.001). Obesity, measured as Body Mass Index (BMI), showed an inverse association with Cd concentrations (β = −0.038, p < 0.001). Egg consumption ≥2 portions/week (β = 0.241, p = 0.025) was positively associated with Cd concentrations. Perceived exposure to paints was also positively associated with Cd concentrations. The observed associations with age, smoking habit, BMI, and egg and meat consumption did not substantially change after sex/gender stratification. Our results are consistent with currently-known Cd sources and suggest other potential pathways, which might be population-specific.As a whole, our findings underline the potential relevance of adipose tissue as a biological matrix for exposure characterization to Cd, as well as for the assessment of long-term clinical implications of the exposure, particularly in obesity-related diseases.

Long-Term Whole Grain Wheat and Rye Intake Reflected by Adipose Tissue Alkylresorcinols and Breast Cancer: A Case-Cohort Study.

Whole grain rye (WGR) and whole grain wheat (WGW) have been suggested to protect against the development of breast cancer. In this study, we estimated long-term intake of WGR and WGW, using both a food frequency questionnaire (FFQ) and alkylresorcinol concentrations in adipose tissue biopsies, in relation to the risk of developing invasive breast cancer in a case-cohort study (n = 414 in the case group, n = 933 in the subcohort group) on the Danish “Diet, Cancer and Health” cohort. The median follow-up time of the subcohort was 5.3 years. Total WGR and WGW intake estimated with FFQ or reflected by total alkylresorcinol concentration in adipose tissue was not significantly associated with risk of breast cancer. However, after adjustment for total WGR and WGW intake, women in the highest quartile of relative WGR intake, reflected by the alkylresorcinol C17:0/C21:0 ratio, had a higher risk of overall breast cancer and estrogen-receptor-positive (ER+) breast cancer than women in the lowest quartile of relative WGR intake, while the risk of estrogen-receptor-negative (ER-) breast cancer incidence was unaffected. Similar results were obtained with the FFQ data. Based on these data, further investigation of the role of specific grain types in reducing or increasing breast cancer risk, and their overall impact on health, is warranted.

Aging Alters Phenotypic Traits of Thyroid Dysfunction in Male Mice With Divergent Effects on Complex Systems but Preserved Thyroid Hormone Action in Target Organs.

Clinical manifestation of hyperthyroidism and hypothyroidism vary with age, with an attenuated, oligosymptomatic presentation of thyroid dysfunction (TD) in older patients. We asked, whether in rodents TD phenotypes are influenced by age and whether this involves changes in systemic and/or organ thyroid hormone (TH) signaling. Chronic hyper- or hypothyroidism was induced in male mice at different life stages (5, 12, and 20 months). TH excess resulted in pronounced age-specific body weight changes (increase in youngest and decrease in old mice), neither explained by changes in food intake (similar increase at all ages), nor by thermogenic gene expression in brown adipose tissue (BAT) or TH serum concentrations. Relative increase in body temperature and activity were more pronounced in old compared to young hyperthyroid mice. An attenuated hypothyroid state was found in old mice for locomotor activity and in heart and BAT on functional (less bradycardia) and gene expression level (heart and BAT). In contrast, decrease in body weight was pronounced in old hypothyroid mice. Thus, age has divergent impact on features of TD in mice, whereby effects on highly complex systems, such as energy homeostasis are not proportional to serum TH state, in contrast to organ-specific responses in heart and BAT.

The effect of cannabinoid receptor 1 blockade on adipokine and proinflammatory cytokine concentration in adipose and hepatic tissue in mice with nonalcoholic fatty liver disease.

In high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD), there is an increase in the endocannabinoid system activity, which significantly contributes to steatosis development. The aim of our study was to investigate the effects of cannabinoid receptor type 1 blockade on adipokine and proinflammatory cytokine content in adipose and hepatic tissue in mice with NAFLD. Male mice C57BL/6 were divided into a control group fed with a control diet for 20 weeks (C, n = 6) a group fed with a HFD for 20 weeks (HF, n = 6), a group fed with a control diet and treated with rimonabant after 18 weeks (R, n = 9), and a group fed with HFD and treated with rimonabant after 18 weeks (HFR, n = 10). Rimonabant significantly decreased leptin, resistin, apelin, visfatin, interleukin 6 (IL-6), and interferon-γ (IFN-γ) concentration in subcutaneous and visceral adipose tissue in the HFR group compared to the HF group (p < 0.01). Rimonabant reduced hepatic IL-6 and IFN-γ concentration as well as plasma glucose and insulin concentration and the homeostatic model assessment index in the HFR group compared to the HF group (p < 0.01). It can be concluded that the potential usefulness of CB1 blockade in the treatment of HFD-induced NAFLD is due to modulation of the adipokine profile and proinflammatory cytokines in both adipose tissues and liver as well as glucose metabolism.

Metabolic Status of Dairy Cows Grouped by Anabolic and Catabolic Indicators of Metabolic Stress in Early Lactation

Background: Early lactation is period followed by changed metabolism in organism of the cow. This is the consequence of negativ energy balance, metabolic stress and milk production. Early lactation is characterised by high lipide catabolism (high NEFA) and low anabolic capacity (low insulin and IGF-I concentration). The aim of this study is to examine differences in metabolic adaptation of cows in early lactation (eight weeks after calving) in accordance to anabolic (insulin, IGF-I) and catabolic (NEFA) indicators in first week after calving.Materials, Methods &amp; Results: The experiment included 50 Holstein-Friesian cows. Blood samples were collected in first, second, fourth and eight week after calving by venepunction of v.coccigea. Based on median value of indicator, cows were significantly (P &lt; 0.001) classified in two groups: cows under metabolic stress (indicators of anabolism below the median Me-: indicators of catabolism above the medianMe+) and cows in control group (indicators of anabolism above the median Me+: indicators of catabolism under median Me-). Following criteria for comparison were given: based on classification of cows according to one indicator of metabolic load (insulinMe-:insulinMe+; IGF-IMe-:IGF-IMe+ and NEFAMe-:NEFA Me+); based on classification of cows according to combination of two indicators (insulinMe-+NEFAMe+: insulinMe++NEFAMe- and IGF-IMe-+NEFAMe+:IGF-IMe++NEFAMe-). Cows loaded with metabolic stress showed significan difference in metabolic adaptation in relation to control group (P &lt; 0.05 or P &lt; 0.01): higher values of STH, BHB (criteria were insulin, IGF-I, NEFA, insulin+NEFA, IGF-I+NEFA), higher values of bilirubin, AST, ALT, GGT, AP (criteria NEFA and IGF-I+NEFA) and MDA (criteria NEFA) and lower levels of glucose, total proteins, albumin (criteria IGF-I, NEFA, IGF-I+NEFA and body condition (criteria insulin, IGF-I, NEFA, insulin+ NEFA, IGF-I+ NEFA) were noted. Differences were expressed the most in first two weeks after calving. Differences in the body condition were the most notable later in weeks. Usage of NEFA indicator in first week after calving allows the most quality recognition of cows with metabolic parameters in extreme quartiles (ROC AUC= 0.87, P &lt; 0.01) in first eight week of lactation.Discussion: Inverse relation betwen NEFA with insulin and IGF-I is consequence of next phisiological concept: plasma insulin and IGF-I decrease in same mannure after calvig and insulin aplication increase IGF-I; low insulin concentration leads cow to lipolysis and low IGF-I leads to STH resistance with increase concentration of STH and high lipolysis. Catabolism of adipose tissue and high NEFA concentration is most important for metabolic adaptation in periparturient period. Cows with insulin resistance, ketosis and fatty liver with many problems in metabolic adaptation showed high NEFA concentration. Atenuation of NEFA by niacin or anti-inflammatory drug decreases metabolic change due to high lipide mobilisation in early lactation. Low antepartal IGF-I showed significant effect on postpartum health, but our measuremens are in first week postpartum. In addition, increase catabolism of lipide viewed in NEFA value contributes to metabolic variation and adaptation in the first eight weeks of lactation much more than decrease of anabolic indicators such as insulin and IGF-I. The combination of the indicators does not lead to better recognition of cows with extreme metabolic change in relation to classification only to the value of NEFA.

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.