Assaf Rudich - Academia.edu (original) (raw)

Papers by Assaf Rudich

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

Obesity Surgery

DiaRem is a clinical scoring system designed to predict diabetes remission (DR) 1-year post-Roux-... more DiaRem is a clinical scoring system designed to predict diabetes remission (DR) 1-year post-Roux-en-Y gastric bypass (RYGB). We examined long-term (2- and 5-year) postoperative DR prediction by DiaRem and an advanced-DiaRem (Ad-DiaRem) score following RYGB, sleeve gastrectomy (SG), and gastric banding (GB). We accessed data from a computerized database of persons with type 2 diabetes and BMI ≥ 30 kg/m who underwent RYGB, SG, or GB, and determined DR status 2- and 5-year postoperative according to preoperative DiaRem and the Ad-DiaRem calculated scores. Among 1459 patients with 5-year postoperative diabetes status data, 53.6% exhibited DR. For RYGB, Ad-DiaRem trended to exhibit mildly improved predictive capacity 5-year postoperatively compared to DiaRem: Areas under receiver operating characteristic [AUROC] curves were 0.85 (0.76-0.93) and 0.78 (0.69-0.88), respectively. The positive predictive values (PPVs) detecting > 80% of those achieving DR (i.e., sensitivity ≥ 0.8) were 78.2% and 73.2%, respectively, and higher Ad-DiaRem scores more consistently associated with decreased DR rates. Following SG, both scores had an AUROC of 0.82, but Ad-DiaRem still had a higher PPV for predicting > 80% of those with 5-year postoperative DR (76.2% and 71.0%). Predictive capacity parameters were comparatively lower, for both scores, when considering DR 5-year post-GB (AUROC: 0.73 for both scores, PPV: 66.3% and 64.3%, respectively). Ad-DiaRem provides modest improvement compared to DiaRem in predicting long-term DR 5-years post-RYGB. Both scores similarly provide fair predictive capacity for 5-year postoperative DR after SG.

Environmental pollution (Barking, Essex : 1987), 2018

Obesity and exposure to particular matter (PM) have become two leading global threats to public h... more Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challe...

European journal of clinical nutrition, Jan 29, 2018

The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous obs... more The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis. In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound. Carotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, -1.4 (17.0) mm, ...

Clinical nutrition ESPEN, 2018

The ability to mobilize pancreatic-fat and the meaning of decreased fat in the pancreas remain co... more The ability to mobilize pancreatic-fat and the meaning of decreased fat in the pancreas remain controversial. We followed the dynamics of pancreatic-fat and its morphology during various long weight-loss induced lifestyle-interventions. In isolated workplace with monitored/provided lunch, we randomly assigned healthy persons with abdominal obesity or dyslipidemia for one of two 18-month equal-caloric diets: low-fat (LF) or Mediterranean/low-carbohydrate (Med/LC, with provided 1oz walnuts/day), with or without added moderate exercise (supervised gym membership). We used magnetic-resonance-imaging to quantify pancreatic-fat and morphology. At baseline, 277 eligible participants (mean age = 48 years; 88% men; pancreatic-fat = 17.4 ± 5.1%) had higher pancreatic-fat in men (17.7 ± 4.9% vs 14.9 ± 5.5% in women; p = 0.004). Following 18-month intervention (adherence = 86.3%) and moderate weight-loss (mean = -3.0 ± 5.5 kg), pancreatic-fat decreased moderately but significantly (-0.26 ± 2.18...

Circulation, Jan 15, 2017

Background -We aimed to assess whether distinct lifestyle strategies can differentially affect sp... more Background -We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. Methods -We performed an eighteen-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to iso-caloric low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet+28g walnuts/day with/without added moderate physical activity (PA;80% aerobic; supervised/free gym membership). Overall primary outcome was body fat re-distribution, and the main specific endpoint was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots [deep/superficial subcutaneous (D/SSAT), liver, pericardial, muscle, pancreas and renal-sinus] by magnetic-resonance-imaging. Results -Of 278 participants (age=48y; 89%men, body-mass-index=30.8kg/m2), 86% completed the trial, with good adherence. The LF group preferentially decre...

Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jan 27, 2017

Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin ... more Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1-7. Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages. Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1-7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1-7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation. Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay. Conditioned media of macrophages treated with OPN-C induced hcECs' NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1-7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to an...

Molecular Metabolism

OBJECTIVE: Obesity variably disrupts human health, but molecular-based patients' healthrisk strat... more OBJECTIVE: Obesity variably disrupts human health, but molecular-based patients' healthrisk stratification is limited. Adipose tissue (AT) stresses may link obesity with metabolic dysfunction, but how they signal in humans remains poorly-characterized. We hypothesized that a transcriptional AT stress-signaling cascade involving E2F1 and ASK1 (MAP3K5) molecularly defines high-risk obese subtype. METHODS: ASK1 expression in human AT biopsies was determined by real-time PCR analysis, and chromatin immunoprecipitation (ChIP) adopted to AT explants was used to evaluate the binding of E2F1 to the ASK1 promoter. Dual luciferase assay was used to measure ASK1 promoter activity in HEK293 cells. Effects of E2F1 knockout/knockdown in adipocytes was assessed utilizing mouseembryonal-fibroblasts (MEF)-derived adipocyte-like cells from WT and E2F1-/-mice and by siRNA, respectively. ASK1 depletion in adipocytes was studied in MEF-derived adipocyte-like cells from WT and adipose tissue-specific ASK1 knockout mice (ASK1-ATKO). RESULTS: Human visceral-AT ASK1 mRNA (N = 436) was associated with parameters of obesity-related cardio-metabolic morbidity. Adjustment for E2F1 expression attenuated the association of ASK1 with fasting glucose, insulin resistance, circulating IL-6, and lipids (triglycerides, HDL-cholesterol), even after adjusting for BMI. Chromatinimmunoprecipitation in human-AT explants revealed BMI-associated increased occupancy of the ASK1 promoter by E2F1 (r2 = 0.847, p < 0.01). In adipocytes, siRNA-mediated E2F1-knockdown, and MEF-derived adipocytes of E2F1-knockout mice, demonstrated decreased ASK1 expression and signaling to JNK. Mutation/truncation of an E2F1 binding site in hASK1 promoter decreased E2F1-induced ASK1 promoter activity, whereas E2F1-mediated sensitization of ASK1 promoter to further activation by TNF was inhibited by JNK-inhibitor. Finally, MEF-derived adipocytes from adipocyte-specific ASK1knockout mice exhibited lower leptin and higher adiponectin expression and secretion, and resistance to the effects of TNF. CONCLUSIONS: AT E2F1-ASK1 molecularly defines a metabolically-detrimental obese sub-phenotype. Functionally, it may negatively affect AT endocrine function, linking AT stress to whole-body metabolic dysfunction.

The American Journal of Clinical Nutrition

Background: In view of evidence linking pericardial fat accumulation with increased cardiovascula... more Background: In view of evidence linking pericardial fat accumulation with increased cardiovascular disease risk, strategies to reduce its burden are needed. Data comparing the effects of specific long-term dietary interventions on pericardial fat tissue mobilization are sparse.Objective: We sought to evaluate intrapericardial-fat (IPF) and extrapericardial-fat (EPF) changes during weight-loss interventions by different dietary regimens.Design: During 18 mo of a randomized controlled trial, we compared a Mediterranean/low-carbohydrate (MED/LC) diet plus 28 g walnuts/d with a calorically equal low-fat (LF) diet among randomly assigned participants with moderate abdominal obesity. We performed whole-body MRI and volumetrically quantified IPF and EPF among 80 participants to follow the 18-mo changes.Results: The participants [mean age: 48.6 y; mean body mass index (BMI; in kg/m2); 31.7; 90% men] had baseline IPF and EPF (mean ± SD) volumes of 172.4 ± 53.3 mL and 194.9 ± 71.5 mL, respectively. The 18-mo moderate weight loss of 3.7 kg was similar in both groups, but the reduction in waist circumference was higher in the MED/LC group (-6.9 ± 6.6 cm) than in the LF diet group (-2.3 ± 6.5 cm; P = 0.01). After 18 mo, the IPF volume had reduced twice as much in the MED/LC group compared with the LF group [-37 ± 26.2 mL (-22% ± 15%) compared with -15.5 ± 26.2 mL (-8% ± 15%), respectively; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, after adjustment for changes in weight or visceral adipose tissue]. The EPF volume had reduced similarly in both groups [-41.6 ± 30.2 mL (-23% ± 16%) in the MED/LC group compared with -37.9 ± 28.3 mL (-19% ± 14%) in the LF group; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.1]. After controlling for weight loss, IPF and EPF volume reduction paralleled changes in lipid profile but not with improved glycemic profile variables: the IPF relative reduction was associated with a decrease in triglycerides (TGs) (β = 0.090; 95% CI: 0.026, 0.154; P = 0.007) and the ratio of TGs to high-density lipoprotein (HDL) cholesterol (β = 2.689; 95% CI: 0.373, 5.003; P = 0.024), and the EPF relative reduction was associated with an increase in HDL cholesterol (β = -0.452; 95% CI: -0.880, -0.023; P = 0.039) and a decrease in total cholesterol and HDL cholesterol (β = 3.766; 95% CI: 1.092, 6.440; P = 0.007).Conclusions: Moderate but persistent dietary-induced weight loss substantially decreased both IPF and EPF volumes. Reduction of pericardial adipose tissues is independently associated with an improved lipid profile. The Mediterranean diet, rich in unsaturated fats and restricted carbohydrates, is superior to an LF diet in terms of the IPF burden reduction. This trial was registered at clinicaltrials.gov as NCT01530724.

Diabetologia

Aims/hypothesis Not all people with type 2 diabetes who undergo bariatric surgery achieve diabete... more Aims/hypothesis Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem]). Methods We used a retrospective French cohort (n = 1866) that included 352 individuals with type 2 diabetes followed for 1 year post-RYGB. We developed the Ad-DiaRem in a test cohort (n = 213) and examined its accuracy in independent cohorts from France (n = 134) and Israel (n = 99). Results Adding two clinical variables (diabetes duration and number of glucose-lowering agents) to the original DiaRem and modifying the penalties for each category led to improved predictive performance for Ad-DiaRem. Ad-DiaRem displayed improved area under the receiver operating characteristic curve and predictive accuracy compared with DiaRem (0.911 vs 0.856 and 0.841 vs 0.789, respectively; p = 0.03); thus correcting classification for 8% of those initially misclassified with DiaRem. With Ad-DiaRem, there were also fewer misclassifications of individuals with mid-range scores. This improved predictive performance was confirmed in independent cohorts. Conclusions/interpretation We propose the Ad-DiaRem, which includes two additional clinical variables, as an optimised tool with improved accuracy to predict diabetes

Clinical nutrition (Edinburgh, Scotland), Jan 2, 2017

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during w... more Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m(2)) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower esti...

Diabetes/Metabolism Research and Reviews, 2017

Intrahepatic-fat (IHF) is best known to associate with waist circumference (WC) and visceral-adip... more Intrahepatic-fat (IHF) is best known to associate with waist circumference (WC) and visceral-adipose-tissue (VAT), but its relation to abdominal subcutaneous-adipose tissue (SAT) is controversial. While IHF &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 5% dichotomously defines fatty liver, %IHF is rarely considered as a continuous variable that includes the normal range. In this study, we aimed to evaluate %IHF association with abdominal fat sub-depots, pancreatic and renal-sinus fats. We evaluated %IHF, abdominal fat sub-depots, %pancreatic and renal-sinus fats, among individuals with moderate abdominal obesity, using 3-T magnetic resonance imaging (MRI). Among 275 participants, %IHF widely ranged (0.01%-50.4%) and was lower in women (1.6%) than men (7.3%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In an age, sex, and WC-adjusted models, VAT area (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.006) was directly associated with %IHF, while superficial-SAT proportion was inversely associated with %IHF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.006). In these models, renal-sinus fat was positively associated with %IHF (p = 0.005). In an age, sex, WC, and VAT-adjusted models, elevated liver enzymes, glycemic, lipid, and inflammatory biomarkers were associated with increased %IHF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.003 for all). In these models, the associations remained robust even within the normal range strata of IHF &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 5% for triglycerides and chemerin (p ≤ 0.004 for all). For the diagnosis of fatty liver, the joint Area Under the Curve of WC, alanine-aminotransferase, triglycerides/HDL-c and homeostasis-model-assessment of insulin resistance (HOMA-IR) was 0.84(95% CI 0.79-0.89). Intrahepatic-fat is differentially associated with abdominal fat sub-depots. Intrahepatic-fat as a continuous variable could be predicted by specific traditional parameters, even within the current normal range, and partially independent of VAT.

Public Health Nutrition, 2016

Objective To generate evidence-based conclusions about the effect of wine consumption on weight g... more Objective To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes. Design In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI. Setting Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel. Subjects Alcohol-abstaining adults with well-controlled type 2 diabetes. Results Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Change...

PLOS ONE, 2016

Background Visceral adipose tissue foam cells are increased in human obesity, and were implicated... more Background Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient. Methods We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery. Results Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditionedmedia. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250, p<0.05) and ATM lipid content (r = 0.303,p<0.05). Among patients with BMI25Kg/m 2 , linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men.

Journal of Applied Physiology, 2016

It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whe... more It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whether it is merely a marker of abnormalities, as well as what are the effects of specific lifestyle strategies for weight loss on the dynamics of both IMAT and thigh muscle area (TMA). We followed the trajectory of IMAT and TMA during 18-mo lifestyle intervention among 278 sedentary participants with abdominal obesity, using magnetic resonance imaging. We measured the resting metabolic rate (RMR) by an indirect calorimeter. Among 273 eligible participants (47.8 ± 9.3 yr of age), the mean IMAT was 9.6 ± 4.6 cm2. Baseline IMAT levels were directly correlated with waist circumference, abdominal subdepots, C-reactive protein, and leptin and inversely correlated with baseline TMA and creatinine ( P < 0.05 for all). After 18 mo (86.3% adherence), both IMAT (−1.6%) and TMA (−3.3%) significantly decreased ( P < 0.01 vs. baseline). The changes in both IMAT and TMA were similar across the lif...

Diabetologia, 2001

Aims/hypothesis: Adipose tissue lipolysis plays a central part in total body fuel metabolism. Our... more Aims/hypothesis: Adipose tissue lipolysis plays a central part in total body fuel metabolism. Our study was to assess the long-term regulation of glycerol and non-esterified fatty acid (NEFA) release by insulin or TNF-alpha. Methods: Fully differentiated 3T3-L1 adipocytes were exposed for up to 22 h to insulin or TNF-alpha. Results: Long-term insulin treatment resulted in increased basal glycerol release, reaching sixfold at 22 h with 1 nmol/l insulin. Partial inhibition was observed by pharmacologically inhibiting phosphatidylinositol 3-kinase or the mitogen-activated kinase kinase--extracellular signal-regulated kinase cascades. This represented 50-60% of the response induced by 1 nmol/l TNF-alpha and approximately 40 % of the glycerol release maximally stimulated by isoproterenol (1 micromol/l, 30 min). The cellular mechanism seemed to be distinct from that of TNF-alpha: First, glycerol release in response to long-term insulin was progressive with time and did not display a lag-time characteristic of the effect of TNF-alpha. Second, pretreatment and co-treatment of the cells with troglitazone greatly inhibited TNF-alpha-induced glycerol release (128.5 +/- 10.2 to 35.4 +/- 2.1 nmol/mg protein per h) but not the effect of insulin, which was exaggerated. Third, hormone-sensitive lipase protein content was decreased (45 %) by TNF-alpha but not following long-term insulin. Finally, TNF-alpha was associated with NEFA release to the medium, whereas long-term insulin treatment was not. Moreover, glycerol release during isoproterenol-stimulated lipolysis was additive to the effect of long-term insulin, whereas NEFA release was inhibited by nearly 90 %. CONCLUSIONS INTERPRETATION: Contradictory to its short-term inhibitory effect, long-term insulin stimulates glycerol release with concomitant stimulation of NEFA re-esterification.

Endocrinology, 2010

Central obesity is frequently associated with adipose tissue inflammation and hepatic insulin res... more Central obesity is frequently associated with adipose tissue inflammation and hepatic insulin resistance. To identify potential individual mediators in this process, we used in vitro systems and assessed if insulin resistance in liver cells could be induced by secreted products from adipocytes preexposed to an inflammatory stimulus. Conditioned medium from 3T3-L1 adipocytes pretreated without (CM) or with TNF␣ (CM-TNF␣) was used to treat Fao hepatoma cells. ELISAs were used to assess the concentration of several inflammatory mediators in CM-TNF␣. CM-TNF␣-treated Fao cells exhibited about 45% diminution in insulin-stimulated phosphorylation of insulin receptor, insulin receptor substrate proteins, protein kinase B, and glycogen synthase kinase-3 as compared with CM-treated cells, without changes in the total abundance of these protein. Insulin increased glycogenesis by 2-fold in CM-treated Fao cells but not in cells exposed to CM-TNF␣. Expression of IL-1␤ mRNA was elevated 3-fold in TNF␣-treated adipocytes, and CM-TNF␣ had 10-fold higher concentrations of IL-1␤ but not TNF␣ or IL-1␣. IL-1␤ directly induced insulin resistance in Fao, HepG2, and in primary rat hepatocytes. Moreover, when TNF␣-induced secretion/production of IL-1␤ from adipocytes was inhibited by the IL-1 converting enzyme (ICE-1) inhibitor II (Ac-YVAD-CMK), insulin resistance was prevented. Furthermore, liver-derived cells treated with IL-1 receptor antagonist were protected against insulin resistance induced by CM-TNF␣. Finally, IL-1␤ secretion from human omental fat explants correlated with body mass index (R 2 ϭ 0.639, P Ͻ 0.01), and the resulting CM induced insulin resistance in HepG2 cells, inhibitable by IL-1 receptor antagonist. Our results suggest that adipocyte-derived IL-1␤ may constitute a mediator in the perturbed cross talk between adipocytes and liver cells in response to adipose tissue inflammation.

Amer J Obstet Gynecol, 2011

In a cohort of women with a high prevalence of optimal levels of serum 25(OH)D, vitamin D status ... more In a cohort of women with a high prevalence of optimal levels of serum 25(OH)D, vitamin D status was not associated with gestational diabetes mellitus. Studies in pregnant populations where vitamin D deficiency is more prevalent are needed to determine the role of vitamin D in gestational diabetes mellitus.

Environmental research, Jan 14, 2016

In this study we investigated the possible causal role for soluble metal species extracted from r... more In this study we investigated the possible causal role for soluble metal species extracted from roadway traffic emissions in promoting particulate matter (PM)-induced reactive oxygen species (ROS) production and antioxidant response element (ARE) promoter activation. To this end, these responses have been evaluated in alveolar macrophage and epithelial lung cells that have been exposed to 'Unfiltered', 'Filtered' and 'Filtered+Chelexed' water extracts of PM samples collected from the roadway urban environments of Thessaloniki, Milan and London. Except for Thessaloniki, our results demonstrate that filtration resulted in a minor decrease in ROS activity of the fine PM fraction, suggesting that ROS activity is attributed mainly to water-soluble PM species. In contrast to ROS, ARE activity was mediated predominantly by the water-soluble component of PM present in both the fine and coarse extracts. Further removal of metals by Chelex treatment from filtered water...