Increased Serum TG Research Articles

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.

Potential Value of Serum Lipid in the Identication of Postoperative Delirium Undergoing Knee/Hip Arthroplasty: The Perioperative Neurocognitive Disorder and Biomarker Lifestyle Study.

ObjectiveWe aimed to investigate the relationship between preoperative lipid level and postoperative delirium (POD) and explore whether lipid’s effect on POD is mediated by POD core protein.MethodsA total of 635 patients who were planned to undergo knee/hip arthroplasty under combined spinal-epidural anesthesia, regardless of gender, were selected. The patients were aged 40–90 years with American Society of Anesthesiologists physical status I II. The Mini-Mental State Examination (MMSE) was completed 1 day before the operation. Five milliliter elbow venous blood was taken from the patients before anesthesia, and serum levels of total cholesterol (TG), triglyceride (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were detected. Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural combined puncture, and amyloid beta40 (Aβ40), amyloid beta42 (Aβ42), total Tau (t-Tau), and phosphorylated Tau (p-Tau) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). After the operation, the occurrence and severity of POD were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and NPOD group. Logistic regression was used to analyze the relationship between POD and TC, TG, LDL-C, and HDL-C, and the mediating effect was used to analyze the role of POD core proteins in the relationship between lipid and MDAS. We used the receiver operating characteristic (ROC) and the precision-recall curve (PRC) analysis to assess the ability of TC, TG, LDL-C, and HDL-C ability to predict POD. Finally, we performed a sensitivity analysis to assess the stability of the results.ResultsA total of 562 patients were finally enrolled in this study, and 66 patients developed POD, with an incidence of 11.7%. Logistic regression analysis showed that high concentration of TC (OR = 3.148, 95%CI 1.858∼5.333, P < 0.001), TG (OR = 2.483, 95%CI 1.573∼3.918, P < 0.001), and LDL-C (OR = 2.469, 95%CI 1.310∼4.656, P = 0.005) in serum were risk factors for POD. A high concentration of HDL-C (OR = 0.258, 95%CI 0.112∼0.594, P = 0.001) was a protective factor for POD after adjusted for age, sex, education, and MMSE score. ROC curves showed that HDL-C have the highest sensitivity and specificity in predicting POD. For these four lipid markers, the PRC range from 0.602 to 0.731, respectively. The mediating analysis showed that POD core proteins could partially mediate the relationship between lipid and POD (effect value: 16.19∼91.04%). The results were barely changed in the sensitivity analysis, and the sensitivity analysis has shown that the results were stable.ConclusionThe increase of serum TG, TC, and LDL-C concentration is a risk factor for POD development, while high HDL-C concentration is a protective factor for POD, and the occurrence of POD is caused by hyperlipidemia may be caused by POD core proteins.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [Chictr200033439].

Outcomes after radioiodine ablation in patients with thyroid cancer: Long-term follow-up of a Chinese randomized clinicaltrial.

Two large randomized trials of patients with differentiated thyroid cancer (DTC) reported recently (HiLo and ESTIMABL1) found that the recurrence rate among patients who underwent 1.1 GBq radioactive iodine (RAI) ablation was not higher than that of patients who underwent 3.7 GBq radioactive iodine (RAI) ablation. However, no similar studies have been conducted in China. We aimed to report clinical outcomes in Chinese patients with low/intermediate risk of recurrence DTC after long-term follow-up, and evaluate the risk factors that influence the presence or absence of incomplete response at the final follow-up. A long-term follow-up of a Chinese randomized clinical trial (October 2014 and February 2021) was conducted. A total of 506 DTC patients at low/intermediate risk of recurrence who were randomized into two groups to receive 1.1(n = 251) or 3.7 GBq (n = 255) RAI ablation following thyroid hormone withdrawal were followed on levothyroxine treatment for a median of 4.5 years (range: 1.6-6.3). Suppressed serum thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels were determined, and neck ultrasonography was performed. At the final follow-up, 499 (98.6%) patients showed an excellent response. The other seven patients (two patients underwent 1.1 GBq and five patients underwent 3.7 GBq RAI ablation, respectively) showed either structural incomplete response (lymph node metastasis, n = 1), biochemical incomplete response (increased serum Tg ≥ 1 ng/ml, or increased positive TgAb levels, n = 5), or indeterminate response (stable positive TgAb levels, n = 1). The risk of incomplete response at the final follow-up was significantly increased in patients with stimulated serum Tg ≥ 10 ng/ml at ablation (p = .003) and in patients with unsuccessful ablation (p = .008). Our findings indicated that there was no difference in the long-term outcomes with RAI ablation using either 1.1or 3.7 GBq in patients with low/intermediate risk of recurrence DTC, and 1.1 GBq RAI might be suitable for patients who are recommended for ablation.

A Study of the Impact of Treatment Response to Direct Acting Antivirals on Serum Lipid Profile in Egyptian Patients with Chronic HCV Infection

AbstractBackground: Hepatitis C virus infection is a major etio-logical factor for liver cirrhosis, steatosis, and hepatocellular carcinoma. HCV is known to be closely related and associated with host and lipid metabolism.Aim of Study: This study aimed at studying the changes in serum lipid profile with INF-free treatment regimens in chronic HCV infection.Patients and Methods: This prospective observational cohort study was carried out on 301 chronic HCV-infected patients, who had fulfilled the inclusion & exclusion criteria and treated according to the National Committee of Control of Viral Hepatitis (NCCVH) Treatment Protocol, updated in December 2016, and completed their course of treatment and follow-up. They were divided into two groups. Group I included 264 patients, who achieved SVR and Group II included 37 patients who did not achieve SVR. Patients underwent additional investigations in the form of 12h fasting serum lipids profile (mg/dl) including: Serum cholesterol, serum triglycerides, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL). These tests were done before starting treatment (baseline), at the end of treatment.Results: There was a statistically significant difference between responder and non-responder groups as regard baseline cholesterol (p=0.001), LDL (p=0.001), HDL (p=0.026) and triglycerides levels (p=0.016). These lipid parameters increased significantly over the course of the therapy and continued to be increased after treatment discontinuation in responders; while they showed non-significant changes in non-responders.Conclusions: Viral eradication was associated with in-creased serum cholesterol, TG & LDL levels, which continued to be elevated after discontinuation of therapy.

Changes in liver perilipin gene expression during an oral lipid load in obese OLETF rats

Non‐alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver maladies in the US. NAFLD is associated with obesity, hyperlipidemia, hypertension, insulin resistance, and diabetes; all traits linked to metabolic syndrome, affecting 20% of the US population. Inappropriate hepatic lipid accumulation is associated with metabolic syndrome. Intracellular lipid storage is regulated by lipid droplets (LDs) that are active components of the cell. LDs have surface proteins of which the most studied belong to the PAT family (Perilipin1–5), which participate in storage and lipid metabolism. To evaluate the effect that a high‐lipid load on the expression and dynamics of hepatic perilipins during early onset T2D, an oral fat tolerance test (OFTT) was performed in 28 wk‐old rats (n=5–6/group): (1) healthy, strain control LETO, and (2) obese, diabetic OLETF. Liver and blood were collected before (T0) and after (T1, T2, T4, and T8 hours) the lipid challenge. An acute increase in serum TG was observed at T2 (p= &lt; 0.0001) and was maintained over the next 6 hours in OLETF whereas in LETO it decreased after the T2 mark. The mRNA expression of Plin2 increased 2.5‐fold in OLETF at T2 compared to LETO, and increased 2.5‐fold at T8 in LETO compared to baseline. Plin3 remained higher (p= 0.0077) in LETO compared to OLETF at T8. Plin4 did not change significantly in response to the lipid challenge between groups. Plin5 increased 1.8‐fold in LETO at T8 compared to baseline. These changes help explain the contributions of LDs to the regulation of hepatic lipids during both normal and diabetic conditions in response to a high lipid challenge similar to the consumption of a high‐fat meal. As Plin2 and 3 have been described as structural LD‐associated proteins, being present mostly in nascent LD, suggesting that a high fat load induces an acute induction of hepatocyte lipid storage. The increase in Plin5 suggests that lipid metabolism pathways are being activated, as Plin5 has been related with mitochondrial FA metabolism. The differential expression patterns of perilipins in response to an acute lipid challenge illustrates the timing of the cellular changes during the development of hepatic steatosis, providing useful insights into future development of treatment by targeting the PAT family of proteins.Support or Funding InformationThis work was supported by NIH's MHRT program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MTOR signaling in adipose tissue influences systemic lipid metabolism

Rapamycin, a fungicidal macrolide, has been shown to increase life span and delay the onset of age related diseases across several model organisms. However, rapamycin treatment leads to metabolic dysregulation including glucose intolerance and hyperlipidemia, which limits its potential utility as an anti‐ageing agent. Rapamycin treatment increases serum triglycerides in human patients by 95%, and while it influences the expression of multiple proteins involved in lipid handling in liver and adipose tissue, the precise mechanism by which rapamycin treatment causes hypertriglyceridemia is not knownRapamycin is an allosteric inhibitor of mTOR (mechanistic target of rapamycin), a serine/threonine protein kinase that functions as a master regulator of cellular growth and metabolism. mTOR exists in two distinct protein complexes, mTORC1 (characterized by the presence of raptor) and mTORC2 (characterized by the presence of rictor), with each complex phosphorylating a distinct set of effector proteins. Rapamycin acutely inhibits mechanistic target of rapamycin complex I (mTORC1), but can also inhibit mTORC2 under chronic conditions. Tissue specific disruption of mTORC1 or mTORC2 has revealed that each complex has different effects on whole body glucose and lipid homeostasis in different organs. Genetic ablation of either mTORC1 or mTORC2 in hepatocytes fails to phenocopy the effects of rapamycin treatment, suggesting that mTOR signaling in another tissue is responsible for rapamycin‐induced hypertriglyceridemia.LPL hydrolyzes the TG in VLDL into FFA for uptake into adipose tissue. In addition, mTORC1 has been shown to inhibit lipolysis and therefore the releases of FFA into plasma. Using adipose specific raptor knockout mice, we show that TG clearance is delayed and LPL gene expression and genes related to LPL processing are altered in the absence of mTORC1 signaling. The decrease in TG clearance can be a result of the decrease in adipose tissue LPL synthesis due to decreased mRNA and/or decreases secretion of active LPL into the blood. This can result in decreased rate of VLDL‐TG hydrolysis and slower clearance of plasma TG, leading to a buildup of TG levels in the blood. In addition, upon refeeding, these KO mice have increased serum TG and FFA, suggesting a failure to suppress lipolysis. Based off phosphoproteomics analysis, phosphorylation of ATGL, the rate limiting enzyme in lipolysis, is increased with loss of mTORC1 in adipose tissue, thus increasing activity of ATGL. ATGL‐Raptor double knockout mice were generated. The DKO mice, upon refeeding, phenocopy control mice serum TG and FFA. This suggest that with loss of mTORC1 there is an increase in lipolysis in adipose tissue when lipolysis should be inhibited, which leads to increased release of FFA and uptake into the liver. This increase leads to an increase in liver TG for increased VLDL‐TG secretion. Decreased LPL activity and increased lipolysis in adipose can both increase plasma TG levels. We hypothesize that inhibition of mTORC1 signaling in adipose tissue is the major driver of hyperlipidemia caused by rapamycin.Support or Funding InformationThis work was supported by grants from the National Institutes of Health (R01‐AG‐043483 and R01‐DK‐098656 to J.A.B.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.

“2-(4-Fluorobenzamido)-4-methylthiazole-5-carboxylic acid” a novel thiazole compound, ameliorates insulin sensitivity and hyperlipidaemia in streptozotocin-induced diabetic rats: Plausible role of inflammatory and oxidative stress markers

Emerging evidence suggests that thiazole compounds are of great interest due to their protective effect against DM. Protective effects of thiazole derivatives against hyperglycemia have been demonstrated in earlier in vitro and in vivo studies. Previously, anti-oxidant and free radical scavenging activities of 2-(4-Fluorobenzamido)-4-methylthiazole-5-carboxylicacid, a newly developed thiazole derivative (NDTD), have been well-documented. Current study investigated the pharmacological effect of NDTD on hyperglycaemia, insulin sensitivity, lipid profile, anti-inflammatory and oxidative stress markers in an animal model. T2DM was induced in neonatal rats using single i.p. injection of STZ at a dose of 100mg/kg. As a result, significant increase in serum glucose, insulin and HOMA-IR, lipid and pro-inflammatory cytokines levels were observed in STZ diabetic rats compared to normal control rats. Administration of NDTD for 4 weeks reversed the increased levels of above mentioned parameters to normal. Increased serum TG, TC, LDL-C and VLDL-C levels were significantly lowered, while reduction of serum HDL-C was alleviated after administration of NDTD. In addition, NDTD attenuated oxidative stress markers by increasing levels of GSH, CAT, SOD and lowering the level of MDA. Similarly, NDTD showed its pharmacological effects against hepatic and renal injury markers via restoring the alleviated level of ALT, AST, BUN, CRE and uric acid. In addition, all the results obtained from the biochemical estimations were supported by the histopathological examination. Pancreatic histopathological study demonstrated reduction in the size of pancreatic islets as well as the number of β-cells, per islet in the STZ control group and diabetic rats exposed to NDTD normalized the morphology of islets. Furthermore, histopathological study of liver suggests the protective role of NDTD against hepatic injury, as diabetic rats exposed with NDTD shows significantly reduction in inflammation and lesion as compared to STZ control rats. Our findings concluded, NDTD attenuated hyperglycaemia, glucose intolerance and insulin resistance through its anti-oxidant and anti-inflammatory effects. Thus, we suggest NDTD as potential therapeutic candidate for T2DM. In addition, the current study also investigated the beneficial effects of NDTD against inflammation, hyperlipidemia, renal and hepatic injury.

MiR-30e-UCP2 pathway regulates alcoholic hepatitis progress by influencing ATP and hydrogen peroxide expression.

To investigate the expression of miR-30e-UCP2 pathway in different stages of alcoholic liver disease (ALD) and its capacity and mechanism in regulating alcoholic hepatitis (AH) progress. C57BL/6 mice were fed with Lieber-DeCaril (LD) diet for 4 and 12 weeks to establish models of alcoholic fat infiltration (AFI) and AH. Based on AFI feeding, the alcoholic hepatic fibrosis (AHF) was set up with additional 4 weeks 5% carbon tetrachloride intra-abdominal injection twice per week. Serum lipid and inflammation related makers were detected while H-E staining for hepatic steatosis/ inflammation and Sirius staining for hepatic fibrosis were conducted. The apoptosis degree was tested by TUNEL plot while the hydrogen peroxide (H2O2) and ATP levels were tested by colorimetric method. MiR-30e and UCP2 over-expression were carried out by synthesizing miR-30e mimic and inserting UCP2 sequence into pCDNA3.1 plasmid. Different stages of ALD were established as indicated by increased serum TG, Tch, ALT, AST, apoptosis degree and hyaluronic acid levels as well as the typical lipid deposition, inflammatory cell infiltration and fibrosis formation in AFI, AH and AHF stages. A stepwise decreased miR-30e and increased UCP2 level was identified from AFI to AHF (p<0.05). MiR-30e over-expression significantly decreased UCP2 level. After successful miR-30e over-expression in AH, its inflammation level was decreased, followed by significantly increased ATP and H2O2 levels. Therefore, MiR-30e-UCP2 pathway participates in different stages of ALD and its therapeutic effect on AH may be through influencing oxidative stress and energy metabolism.

Lipid profile in children of β-thalassemia major and their correlation with serum ferritin

Background: β-thalassemia major is a secondary iron load state. The high serum ferritin accounts for abnormal lipid profile. This study was done to investigate the lipid profile in children with β-thalassemia major and to know their correlation with serum ferritin.Methods: Fifty-five (55) children of beta thalassemia major in the age group of 4-20 years from thalassemia unit of tertiary care hospital who were on regular blood transfusion and oral iron chelators were enrolled. Serum ferritin levels and lipid profile of these children were investigated and their correlation was assessed. Results: Out of total 55 children 31 (56.4%) children were of female sex and 48(87.3%) were Hindu by religion. The mean rate of blood transfusion was 157.02±21.33 ml/kg/year with average dose and duration of iron chelation with Desferroxamine was 34.4±26.86 mg/kg /day and 2.34±1.86 years respectively. Mean cholesterol level, high density lipoprotein (HDL), low density lipoprotein (LDL) levels were on lower side of the range with values of 124.47±19.81 mg/dl, 36.58±12.22 mg/dl, 63.94±4.57 mg/dl respectively. The mean triglyceride level (TG) was on higher side with an average of 142.93±33.7 mg/dl. The average serum ferritin levels were 2130.33±859.85 ng/ml. There was negative correlation of total cholesterol, HDL, LDL with serum ferritin with coefficient of correlation (r= -0.77, -0.55, -0.72) respectively. The serum triglyceride had positive correlation with serum ferritin with coefficient of correlation(r=+0.85).Conclusions: As the serum ferritin increases, there occurs more derangement of lipid profile in form of decreasing serum cholesterol, HDL, LDL and increasing serum TG levels.

Evaluation of Thyroid Bed Nodules on Ultrasonography after Total Thyroidectomy: Risk for Loco-Regional Recurrence of Thyroid Cancer

Objectives: We conducted a retrospective chart review of patients with differentiated thyroid cancer who underwent total thyroidectomy to examine the correlation of the persistence of thyroid bed nodules seen on ultrasonography with subsequent loco-regional recurrence. Methods: A total of 60 patients with differentiated thyroid cancer were identified who underwent total thyroidectomy, received ¹³¹I therapy and had thyroid bed nodules on postoperative surveillance ultrasonography. The ultrasonographic features of the thyroid bed nodules and their progression over time along with serum thyroglobulin (Tg) levels were monitored. Those patients who demonstrated no evidence of recurrence were compared to patients who had recurrence. Results: Of the 60 patients, 25% had documented cancer recurrence. Sixty percent of the patients in the recurrence group had an increase in the size of bed nodules as compared to only 7% of the patients in the group without recurrence. An increase in serum Tg of more than 2-fold was seen in 80% of the patients with recurrence and in only 13% (6/45) of the patients without cancer recurrence. The odds of identifying recurrent thyroid cancer in patients with more than a 2-fold increase in serum Tg were 80.5 greater than in patients with a less than 2-fold increase in serum Tg. The odds of identifying recurrent thyroid cancer in patients with the presence of any suspicious thyroid bed nodule were 31.5 times greater than in patients without suspicious thyroid bed nodules. Conclusions: Thyroid bed nodules on surveillance ultrasound warrant fine-needle aspiration cytology if they increase in size and number, are persistent and associated with suspicious sonographic features.

Upregulation of hepatic VLDLR via PPARα is required for the triglyceride-lowering effect of fenofibrate

The liver and the VLDL receptor (VLDLR) play major roles in TG and VLDL metabolism. However, the exact role of liver VLDLR is not well known because of the absence of or difficulty in detecting VLDLR in the liver. In this study, we demonstrate that fenofibrate, a PPARα agonist and widely used TG-lowering drug, markedly upregulated hepatic VLDLR, which is essential for lowering TG. This study also shows that the distinct regulatory roles of PPARα agonists on VLDLR in the liver and peripheral tissues including adipose tissues, heart, and skeletal muscles are due to the pattern of expression of PPARα. The in vivo portion of our study demonstrated that oral fenofibrate robustly increased liver VLDLR expression levels in hyperlipidemic and diabetic mice and significantly reduced the increase in serum TG observed in wt mice after feeding with high-fat diet (HFD) but not in Vldlr(-/-) mice or Pparα(-/-) mice. However, overexpression of mouse VLDLR in livers of Vldlr(-/-) mice significantly prevented the increase in serum TG induced by HFD. The in vitro portion of our study showed that fenofibrate upregulated VLDLR transcriptional activity through PPAR response element binding to the VLDLR promoter. The conclusions of our study provide a novel mechanism for the TG-lowering effects of fenofibrate in the treatment of dyslipidemia.

Association between GFOD2 (rs12449157) polymorphism, dietary intake, anthropometric measurements and blood lipids in Mexican Subjects

It has been demonstrated the presence of single nucleotide polymorphisms (SNPs) in the recognition element seed sites of mRNA that are controlled by miRNA. One of this mRNA is the glucose fructose oxidoreductase domain containing 2 enzyme (GFOD2). Thus, the aim of this study was to assess the gene‐diet interaction between GFOD2 SNP, carbohydrate and total fat intake on blood lipids and anthropometric measurements. We studied 261 Mexican subjects, 60 men and 201 women. The frequency of the non‐common allele (G) was 21%. The frequency of homozygous for the non‐common allele (GG) and heterozygous (AG) was 38.8%. Homozygous subjects for the common allele (AA) decreased serum TG and increased BMI as the intake of dietary carbohydrates increased, whereas subjects with the non‐common allele showed the opposite pattern. In contrast, subjects homozygous for the common allele increased serum TG and decreased BMI as the total fat intake increased. Subjects with the non‐common allele showed the opposite pattern. These results indicate that the SNP for GFOD2 gene is a risk factor for the development of metabolic abnormalities associated with Metabolic Syndrome.Grant CONACYT 181685 (to MGC)

NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic β-cells induced by very low-density lipoprotein

In type 2 diabetes, pancreatic β-cells cannot secret enough insulin compensate for insulin resistance, which are often accompanied by abnormality in lipid metabolism such as hypertriglyceridemia. It is reported that oxidative stress is involved in pancreatic β-cell dysfunction. However, molecular mechanisms linking between excessive generations of reactive oxygen species (ROS) and β-cell dysfunction and apoptosis induced by high levels of very low-density lipoprotein (VLDL) are poorly understood. In this study, we test the hypothesis that NADPH oxidase 2 (NOX2)-derived ROS may play a key role in dysfunction and apoptosis of pancreatic β-cell induced by VLDL. Our results show that the ApoCIII transgenic mice displayed increased serum TG levels, enhanced generation of ROS and impaired insulin content in pancreatic β-cells. In vitro, the treatment of pancreatic NIT-1 cells with 1 mg/ml VLDL for 12 h stimulated NOX2-derived ROS generation, decreased expression and secretion of insulin. Furthermore, we found that VLDL induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. In conclusion, our data demonstrate a critical role of NOX2-derived ROS in dysfunction and apoptosis through JNK and p53 pathways in pancreatic β-cells induced by VLDL.

Pregnant French Women Living in the Lyon Area Are Iodine Deficient and Have Elevated Serum Thyroglobulin Concentrations

Iodine deficiency (ID) remains common in Europe, and may be especially detrimental during pregnancy. The aim of our study was to assess iodine status and thyroid function in healthy pregnant women in the Lyon metropolitan area. In a cross-sectional study, healthy pregnant women (n=228) with no history of thyroid disease were consecutively recruited from an obstetric clinic during all trimesters. Thyrotropin (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO) antibodies, thyroglobulin (Tg), and urinary iodine concentration (UIC) (n=100) were measured. Thyroid functions were compared with those in a control group of nonpregnant adults. The median (range) UIC was 81 (8-832) μg/L, and 77% of pregnant women had a UIC <150 μg/L, indicating inadequate iodine intake. Overall, 11% of women had abnormal TSH or anti-TPO. The median FT4 (pmol/L) was 14.9, 12.6, and 11.5 in the first, second, and third trimesters, respectively. The median Tg in pregnant women was 16.2 μg/L, did not differ across trimesters, and was significantly higher than in the control group of nonpregnant adults (11.7 μg/L) (p=0.02). Controlling for maternal age and week of gestation, UIC was not a significant predictor of any of the thyroid function tests. Pregnant women in the Lyon area are iodine deficient and have increased serum Tg concentrations compared with nonpregnant controls, likely due to physiological thyroid hyperstimulation during gestation exacerbated by ID.

Consumption of a Resistant Protein, Sericin, Elevates Fecal Immunoglobulin A, Mucins, and Cecal Organic Acids in Rats Fed a High-Fat Diet

AbstractWe previously reported that consumption of a resistant protein, sericin, reduces colon tumorigenesis, constipation, and serum TG in rodents. The present study was conducted to elucidate the effects of dietary sericin on the intestinal luminal environment in rats fed a high-fat (HF) diet. Rats were fed 300 or 50 g/kg of beef tallow with or without 40 g/kg sericin, a protein purified from cocoons of Bombix mori, for 3 wk. Intestinal luminal variables, including IgA (index of intestinal immune function), mucins (index of barrier function), organic acids, microflora, and secondary bile acids, were measured. Dietary sericin markedly elevated fecal IgA in the HF diet group (3-fold, P < 0.05) but not in the low-fat (LF) diet group. Fecal mucin levels were elevated by sericin intake in the HF diet group (P < 0.05). Cecal organic acids, including acetate, propionate, n-butyrate, and succinate, were significantly lower in the HF diet group compared with the LF diet group. Dietary sericin significantly elevated cecal acetate and n-butyrate in the HF diet group but not in the LF diet group. Compared with the LF diet, the HF diet significantly increased serum TG in the untreated group but not in those fed sericin. The HF diet increased lower density lipoprotein (VLDL + IDL + LDL) cholesterol and it was reduced by sericin intake (P < 0.05). There was an inverse correlation between serum TG and cecal acetate (Spearman rank correlation coefficient = -0.63; P < 0.001). The profile of microflora in cecal digesta and fecal secondary bile acids (a risk factor for colon cancer) did not differ between the HF diet and HF diet with sericin groups. These results suggest a novel and favorable effect of sericin on colon health by modulating intestinal immune and barrier functions and fermentation in rats fed a HF diet.

Relationship between serum thyroglobulin and 18FDG‐PET/CT in 131I‐negative differentiated thyroid carcinomas

The purpose of this study was to assess the relationship between [(18) F]-fluorodeoxyglucose ((18) FDG)-positron emission tomography/CT ((18) FDG-PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated thyroid carcinoma (DTC). Forty-two patients with recurrent DTC and negative Tg antibodies were included in the study. All patients underwent (131) I therapy due to an increasing serum Tg with a corresponding negative (131) I posttreatment whole body scan. The (18) FDG-PET/CT scans were then performed on all patients, serum Tg was measured concurrently, and respective results were compared. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of the (18) FDG-PET/CT examination were 93%, 84%, 93%, 84%, and 90%, respectively. The sensitivity of (18) FDG-PET/CT significantly increased in patients with serum Tg levels ≥4.6 ng/mL (96%) in comparison with patients having lower levels (25%; p < .001). Nonetheless, 3 of 27 patients (11%) with a true-positive (18) FDG-PET/CT still had a Tg <4.6 ng/mL. Although (18) FDG-PET/CT scans are more likely to be positive with pretest Tg levels ≥4.6 ng/mL, 11% of patients with DTC with a lower serum Tg level will still have a positive scan. Our findings are in contrast with the American Thyroid Association (ATA) guidelines, which only recommend to perform (18) FDG-PET/CT in patients with Tg levels >10 ng/mL.

Gemfibrozil Improves Postprandial Hypertriglyceridemia in Patients with Isolated Low HDL

Aim To assess the response of postprandial (PP) hypertriglyceridemia to genfibrozil in healthy male subjects with isolated low HDL-Cholesterol but without the metabolic syndrome (MS). Patients and methods 14 male subjects with isolated low HDL (HDL-C ≤ 33), normal fasting triglycerides and LDL-C levels and without any feature of the MS, were studied. 13 male subjects with HDL-C &gt; 38 mg/dl served as controls. They also had normal fasting triglycerides and LDL-C levels and without any feature of the MS. The 2 groups were statistically similar with respect to age, blood pressure, BMI, body fat composition, waist circumference, waist to hip ratio, fasting insulin, fasting and PP blood sugar, baseline fasting TG level and baseline LDL-C. Postprandial TG levels were measured at 2, 4, and 6 hours following a morning meal. Ten of the patients with PP hypertriglyceridemia were treated with gemfibrozil 600 mg PO twice/day for one month. Results Patients had markedly higher levels of the peak PP TG at 4 hours compared to controls (296.0 ± 37.7 vs. 206.7 ± 29.9 mg/dl; P &lt; 0.05) the other two postprandial levels were also higher in patients but the difference was not significant. Treatment with gemfibrozil significantly decreased the levels of fasting and postprandial TG and increased HDL-C by around 3.6 mg/dl (11.7%) without affecting LDL-C. Conclusion Postprandial increase in serum TG may be present in patients with isolated HDL-C without the MS. Treatment of patients with PP hypertriglyceridemia with gemfibrozil improves the low HDL-C and postprandial rise in TG.

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid Carcinoma

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid CarcinomaThyroid carcinomas are the most common malignant endocrine tumors. Thyroglobulin (Tg), a specific thyroid protein, is the most important tumor marker in thyroid oncology. After total thyroidectomy or radioiodine therapy, detectable or increasing serum Tg levels in patients with differentiated thyroid carcinoma indicate persistence of active thyroid tissue or cancer recurrence. Serum Tg concentration primarily reflects three variables: the mass of differentiated thyroid tissue present; the degree of thyrotropin receptor stimulation and the intrinsic ability of the tumor to synthesize and secrete Tg. Measurement of serum Tg by current immunometric (IMA) and radioimmunological (RIA) assays encounters some methodological problems which can diminish its clinical importance. Discrepancy between the results for Tg using different methods may be caused by: different reference materials, specific properties of the primary and secondary antibodies for antigenic determinants on Tg and diverse binding affinities of these epitopes, together with interference by serum factors (usually antibodies to Tg (TgAb)) with the primary and secondary Tg antibodies from the diagnostic set. In the presence of endogenous TgAb, Tg values measured by immunoradiometric assay (IRMA) and similar assays are usually lower than the real concentrations, while in RIA apparently lower or higher results can be obtained. Falsely low values may lead to delay in necessary treatment, while an inappropriately high Tg value can cause patient anxiety and unnecessary scans. Despite current methodological limitations, serum Tg measurement is a useful test for determining worsening disease and monitoring the effects of therapy in patients who have undergone surgery for differentiated thyroid carcinoma.

Alterations in Serum Thyroid–Related Constituents After Thyroid Fine-Needle Biopsy: A Systematic Review

Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive, and generally safe diagnostic procedure in the management of thyroid nodules. Local pain and minor hematomas are the most common clinical complications, and hemorrhage and fibrosis the most common histological alterations after thyroid FNB. FNB can also trigger biochemical alterations in serum, since it may destroy thyroid follicles. In this review we summarized the biochemical alterations in serum that occur after diagnostic thyroid FNB, aiming to review information that would be potentially useful in interpreting thyroid tests in patients who recently had a thyroid FNB. Computerized advanced search for primary evidence was performed in the PubMed (Public/Publisher MEDLINE) electronic database not limited by publication time and English language. An increase in serum thyroglobulin (Tg) ranging from 35% to 341% occurs in 33-88% of patients subjected to FNB. Serum Tg concentrations typically return to baseline about 2-3 weeks after FNB. The abrupt release of Tg after FNB may induce the production of autoantibodies to Tg and thyroid hormones in a minority of patients. There is little information on the effect of FNB on autoantibodies to thyroid peroxidase. No changes seem to occur in thyroid-stimulating hormone, total thyroxine, free thyroxine, free triiodothyronine (T3), or reverse T3, while controversy exists for T3. The degree of increase in serum Tg after FNB is highly variable and not a predictor of whether the biopsied nodule is benign or malignant. The increase or development of Tg autoantibodies that occurs in some patients does not appear to be of clinical significance. Development of autoantibodies to thyroid hormones may be more likely in patients whose biopsied nodule is benign than malignant, but further studies are required to confirm this. If changes in serum thyroid-stimulating hormone or thyroid hormones are noted in a patient with a history of a recent fine-needle aspiration, they should be investigated since they are not likely to be related to the biopsy.