The relationship between serum superoxide dismutase and thyroid function in obese patients after Laparoscopic sleeve gastrectomy.

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity (n = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n = 112) and high levels of SOD (HSOD, n = 107) according to the median value of SOD levels (183 U/mL). SOD and thyroid hormones were measured and compared at baseline, 3, 6, and 12 months after LSG. The HSOD group had lower body mass index (BMI), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) than the NSOD group (p < 0.001, p = 0.031, p < 0.001, respectively). However, they had higher free triiodothyronine (FT3) and free thyroxine (FT4) (p = 0.019 and p = 0.017, respectively). SOD was significantly negatively associated with TSH and positively associated with FT4. Of all the patients, 22.31% (NSOD: 66.67%; HSOD: 33.33%) had subclinical hypothyroidism (SH), and there were lower SOD levels in the SH group. Preoperative SOD was a protective factor for SH. After LSG, SOD and FT4 levels were increased at 12 months after LSG, however, TSH, FT3, total triiodothyronine (TT3) and TT4 levels decreased compared to the preoperative levels at 3, 6, and 12 months in the SH group. Postoperative changes in FT4 and TT4 levels correlated with changes in SOD levels. SOD, which is correlated with thyroid hormones, protects against SH in patients with obesity. The improvement in thyroid function with SH after LSG may be related to increased SOD levels.

Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1.

BACKGROUND AND AIMS: The functions of liver fatty acid binding protein 1 (FABP1) in the regulation of nonalcoholic fatty liver disease (NAFLD) have been previously established. However, how FABP1 expression is dynamically regulated in metabolic disorders is unclear. Previous studies have reported that ubiquitin proteasome-mediated degradation of FABP1 is involved, but the mechanism remains unknown. METHODS: Dysregulated expression of hepatic FABP1 and Derlin-1 was observed in NAFLD patients. We performed mice hepatic tissue coimmunoprecipitation based mass spectrum assays. Interaction between Derlin-1 and FABP1, and its impact on FABP1 ubiquitination status was evaluated by coimmunoprecipitation. The role of Derlin-1 in lipid deposition was tested using adenovirus-mediated overexpression in C57BL/6 mice, as well as by Derlin-1 overexpression or knockdown in HepG2 cells. RESULTS: As a subunit of the endoplasmic reticulum-associated degradation complex, Derlin-1 was negatively associated with NAFLD patients, interacted with and ubiquitinated FABP1. Derlin-1 suppressed FABP1 levels and inhibited lipid deposition through a FABP1-dependent pathway. Additionally, Trim25, an E3 ubiquitin ligase present in the endoplasmic reticulum, was recruited to promote Derlin-1-related polyubiquitylation of FABP1, thereby creating a ubiquitin-associated network for FABP1 regulation. Derlin-1 overexpression ameliorated hepatic steatosis in both C57BL/6 mice and HepG2 cells, and contributed to attenuated weight gain, lower liver weight, and visceral fat mass. CONCLUSIONS: FABP1 was degraded by Derlin-1 through ubiquitin modification. Negative regulation of FABP1 by Derlin-1 overexpression, suppressed lipid metabolism and alleviated lipid deposition in vivo and in vitro. Hence, Derlin-1 activation in hepatocytes may represent a potential therapeutic strategy for NAFLD.

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

BACKGROUND: The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM. METHODS: We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People's Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4. RESULTS: BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4. CONCLUSIONS: BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.

The Association of Serum Irisin with Impaired Glucose Before and After Laparoscopic Sleeve Gastrectomy in Obesity.

BACKGROUND: To demonstrate the association of irisin levels with impaired glucose before and after laparoscopic sleeve gastrectomy (LSG) in patients with obesity. METHODS: Thirty-six patients with obesity undergoing LSG were included. We tested the irisin levels before and after LSG and conducted an evaluation of baseline irisin levels with elevated glucose as well as irisin changes with weight loss and its association with glucose control after LSG. RESULTS: Anthropometric measurements, body fat index, and metabolic parameters were significantly improved in 3 months following LSG (all p < 0.05). Baseline irisin levels were significantly higher in obesity with elevated fasting glucose than that with normal glucose (2.98 [2.37, 3.63] vs. 3.72 [3.06, 5.32], p = 0.031). After adjustment for sex, gender, and body mass index (BMI), obesity with higher irisin levels was prone to have impaired fasting glucose (OR = 2.499, 95% CI = 1.047-5.964). According to receiver operating characteristic curve analysis, the diagnostic accuracy and sensitivity of baseline irisin levels on impaired fasting glucose were 75% and 77.8%. Irisin levels decreased from 3.29 (2.67, 4.43) to 2.82 (2.41, 3.25) ng/mL (p = 0.009) after LSG. The decreases of weight, BMI, and FFA were more in irisin changes group (△irisin ≥ 0.5) than in no irisin changes group (△irisin < 0.5). And △irisin was negatively associated with postprandial glucose (PG) at 3 months after LSG (0.5 h-PG, r = - 0.478, p = 0.029; 2 h-PG, r = - 0.406, p = 0.017). CONCLUSIONS: Elevated baseline irisin levels indicated the impaired glucose in obesity. The decrease of irisin with weight loss provided more evidence for the contribution of serum irisin secretion by fat mass in obesity.

Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy.

Background: Liver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: We enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG. Results: Serum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011). Conclusions: FABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.

Iron metabolism mediates the relationship between Vitamin C and hepatic steatosis and fibrosis in NAFLD.

Vitamin C (Vit C) and iron metabolism are closely related to metabolic disorders. However, the relation between iron storage protein ferritin and Vit C has not been elucidated. We aimed to investigate the crosstalk between Vit C and ferritin and its implications on non-alcoholic fatty liver disease (NAFLD). Clinical information of 3,614 subjects was obtained from the NHANES Public Data 2017-2018. FibroScan data, which estimates liver steatosis and fibrosis and Vit C, were selected to assess factors influencing NAFLD in this cross-sectional study. Ferritin and Vit C among different categories of liver steatosis and fibrosis were assessed by CAP and E value. Logistic regression and RCS models were used to analyze the correlations. In vitro study in hepG2 were conducted to validate the regulations. Ferritin increased while Vit C decreased with more severe hepatic steatosis and hepatic fibrosis (all P < 0.001). Logistic regression models indicated that increased serum ferritin was a risk factor for NAFLD while increased Vit C was a protective factor for NAFLD and hepatic fibrosis after adjusting the continuous and categorical variables. Vitamin C was negatively associated with ferritin. Further mediation analysis identified that ferritin mediates the impact of Vit C on NAFLD (P < 0.05) and cirrhosis (P < 0.001). The experiments on cellular level suggested Vit C alleviated PA/OA induced steatosis and maintains iron homeostasis through inhibiting PA/OA induced upregulation of iron bound protein ferritin and labile iron pool (LIP) induction in hepG2 cells. In conclusion, Vit C was a protective factor, whereas ferritin was a risk factor for hepatic steatosis and fibrosis. Vitamin C alleviated NAFLD and maintained iron homeostasis via ferritin suppression and LIP induction.

Corrigendum: The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine-Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment.

[This corrects the article DOI: 10.3389/fendo.2022.822423.].

Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents nonalcoholic steatohepatitis.

Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). Hepatic inflammation results from abnormal macrophage activation. We found that FoxO1 links overnutrition to hepatic inflammation by regulating macrophage polarization and activation. FoxO1 was upregulated in hepatic macrophages, correlating with hepatic inflammation, steatosis, and fibrosis in mice and patients with NASH. Myeloid cell conditional FoxO1 knockout skewed macrophage polarization from proinflammatory M1 to the antiinflammatory M2 phenotype, accompanied by a reduction in macrophage infiltration in liver. These effects mitigated overnutrition-induced hepatic inflammation and insulin resistance, contributing to improved hepatic metabolism and increased energy expenditure in myeloid cell FoxO1-knockout mice on a high-fat diet. When fed a NASH-inducing diet, myeloid cell FoxO1-knockout mice were protected from developing NASH, culminating in a reduction in hepatic inflammation, steatosis, and fibrosis. Mechanistically, FoxO1 counteracts Stat6 to skew macrophage polarization from M2 toward the M1 signature to perpetuate hepatic inflammation in NASH. FoxO1 appears to be a pivotal mediator of macrophage activation in response to overnutrition and a therapeutic target for ameliorating hepatic inflammation to stem the disease progression from benign steatosis to NASH.

Vitamin C status and its change in relation to glucose-lipid metabolism in overweight and obesity patients following laparoscopic sleeve gastrectomy.

OBJECTIVES: Aimed to demonstrate the association of VC and metabolism in the obesity or overweight and determine VC changes after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 253 overweight or people with obesity were recruited, including 61 with LSG. They were divided into group A (VC < 34 ug/ml) and group B (VC ≥ 34 ug/ml). Glucose-lipid metabolic parameters were compared, and VC status before and 6 and 12 months after LSG were measured. RESULTS: (1) Body weight, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), waist-to-hip ratio, heart rate (HR), diastolic systolic pressure (DBP), 2-hour postprandial glucose (2h-BG), fasting insulin (FINS), 2-hour postprandial insulin (2h-INS), glycosylated hemoglobin (HBG), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) were higher while high-density lipoprotein (HDL-C) was lower in group A than group B (p < 0.05). (2) VC was negatively correlated with body weight, BMI, NC, WC and HC, HR, SBP, DBP, and 2h-BG, FINS, 2h-INS, HGB, HOMA-IR, TG and FFA, while positively with HDL-C (p < 0.05). (3) Patients with obesity or hypertriglyceridemia or low HDL-C had lower VC than corresponding group. (p < 0.05). (4) Logistic regression analysis showed that VC was the independent risk factor of hypertriglyceridemia, obesity and low HDL-C 5) VC concentrations were slightly increased in 6 months after LSG, and unchanged in 12 months after LSG. CONCLUSION: VC was closely associated with glucose-lipid metabolism, and may play a protective role in metabolic disorders. LSG would not worsen the VC status or deficiency.

Relationship of Vitamin A and Thyroid Function in Individuals With Obesity and After Laparoscopic Sleeve Gastrectomy.

Vitamin A deficiency (VAD) occurs in obesity and may be associated with thyroid dysfunction. We aimed to investigate the association of VA with thyroid function in obesity and after laparoscopic sleeve gastrectomy (LSG). Nine hundred and seventy-six obese subjects were enrolled for this study and were divided into VAD, marginal vitamin A deficiency (MVAD), and vitamin A normal (NVA) groups. VAD was defined as VA ≤ 200 ng/ml, MVAD was defined as VA > 200 but <300 ng/ml, and NVA was defined as VA ≥ 300 ng/ml. Thyroid function was compared among groups and the relationship of VA and thyroid function was analyzed. Two hundred and forty-four of the 976 obese subjects underwent LSG, and the change in thyroid function and VA at 3, 6, and 12 months after surgery was measured. Results showed that 37% of all the subjects had subclinical hypothyroidism (SH), and the SH group had lower VA levels than the non-SH group (P = 0.008). Forty-nine percent of all the subjects had MVAD, 9% had VAD, while the MVAD or VAD group had lower FT4 than the NVA group (P = 0.005 and P = 0.001). The VAD group also had higher TSH than NVA group (P = 0.037). VA was significantly negatively associated with TSH (r = -0.151, P = 0.006) and positively associated with FT4 (r = 0.228, P < 0.001). TSH was significantly decreased at 3, 6, and 12 months (3M: from 4.43 ± 2.70 to 2.63 ± 1.46 mU/l, P < 0.001; 6M: from 4.43 ± 2.70 to 3.84 ± 2.34 mU/l, P = 0.041; 12M: from 4.43 ± 2.70 to 2.85 ± 1.68 mU/l, P = 0.024). After LSG surgery, VA levels were slightly increased, when compared to pre-surgery levels, at 3, 6, and 12 months (3M: from 262.57 ± 68.19 to 410.33 ± 76.55 ng/ml, P = 0.065; 6M: from 262.57 ± 68.19 to 281.36 ± 93.23 ng/ml, P = 0.343; 12M: from 262.57 ± 68.19 to 300.37 ± 86.03 ng/ml, P = 0.083). SH group also had lower TSH and higher VA than the non-SH group at 3 months post-surgery [TSH: -1.4(-2.3, -0.3) vs. -0.2(-0.8, -0.2) mU/l, P < 0.001; VA: 163.99 ± 32.58 vs. 121.69 ± 27.59 ng/ml, P = 0.044]. In conclusion VA, which is related to thyroid hormone production, protects against thyroid dysfunction in obese subjects. The improvement of thyroid function in subjects with SH after LSG may be related to the increased VA levels observed post-surgery. Clinical Trial Registration: ClinicalTrial.gov ID: NCT04548232.

The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine-Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment.

Purpose: To investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment. Methods: A total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed. Results: The rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p < 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81-6.44, p < 0.001), 2.19 (1.16-4.13, p = 0.016), and 2.51 (1.29-4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26-8.68, p = 0.015), 3.20 (1.22-8.42, p = 0.018), and 5.62 (2.25-14.01, p < 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively. Conclusions: In this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.

Lower Baseline Serum Triglyceride Levels Are Associated With Higher Decrease in Body Mass Index After Laparoscopy Sleeve Gastrectomy Among Obese Patients.

Aims: To investigate the predictive value of baseline serum triglyceride (TG) levels for improvements of metabolism after laparoscopic sleeve gastrectomy (LSG). Methods: 112 obese patients [body mass index (BMI) ≥ 35 kg/m2] underwent LSG and with complete information of anthropometric and metabolic parameters were divided into normal TG group (group A) and high TG group (group B), while group A had TG levels ≤ 1.7 mmol/L, and group B had TG levels > 1.7 mmol/L. The post-operative changes (Δ) in metabolic parameters between the two groups were compared. Results: In the whole cohort, the metabolic parameters were significantly improved at 6 months after LSG. BMI and waist circumference (WC) decreased significantly in the two groups. The ΔBMI among group A and group B were 11.42±3.23 vs 9.13±2.77 kg/m2 (p<0.001), respectively. ΔBMI was positively correlated with ΔWC (r=0.696, p<0.001), Δfasting insulin level (r=0.440, p=0.002), Δfasting serum C peptide level (r=0.453, p=0.002), and Δhomeostasis model assessment insulin resistance index (r=0.418, p=0.004) in group A. Compared with group B, group A had a significantly higher odds ratio (OR) of 2.83 (95% confidence interval [CI]1.25-6.38, p=0.012)and 2.73 (95% CI 1.11-6.72, p=0.029) for ΔBMI and ΔWC after adjustment for age and gender, respectively. Conclusions: Obese patients with baseline TG levels under 1.7 mmol/L had greater loss of weight at six months follow-up later LSG. This finding suggests that baseline TG level may have a predictive value for weight loss, at least in the short-term follow-up.

Catalytically Active Site Identification of Molybdenum Disulfide as Gas Cathode in a Nonaqueous Li-CO2 Battery.

Li-CO2 batteries have recently attracted attention as promising candidates for next-generation energy storage devices due to their extremely high theoretical energy density. The real application of Li-CO2 cells involves addressing several drawbacks, including high charging potential, poor coulombic efficiency, and low rechargeability. Molybdenum disulfide supported on carbon nanotubes (MoS2/CNT) with various ratios functioned as a cathode catalyst for Li-CO2 batteries. The optimal MoS2/CNT composite achieved a maximum discharge capacity of 8551 mAh g-1 with a coulombic efficiency of 96.7%. This hybrid also obtained an initial charging plateau of 3.87 V at a current density of 100 mA g-1 with a cutoff capacity of 500 mAh g-1. It provided ideal electrochemical stability of 142 cycles at the current densities of 100 mA g-1, which was comparable with that of some precious metal catalysts. This optimized MoS2/CNT was also cycled at 200 and 400 mA g-1 for 112 and 55 times, respectively. Density functional theory calculations demonstrated that the sulfided Mo-edge (s-Mo-edge) on MoS2 materials showed appropriate adsorption strengths of Li, CO2, and Li2CO3. Moreover, joint results of Raman profiles and extended X-ray absorption fine structure spectra elucidated that the catalytic efficiencies of MoS2/CNT hybrids were proportional to the quantities of exposed s-Mo-edge active sites.

Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Iron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated. OBJECTIVE: We aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity. METHODS: A total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery. RESULTS: (1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, p = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all p < 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (p = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all p < 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all p < 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all p < 0.05). CONCLUSIONS: Overall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.

The Increased Risk of Thyroid Cancer-Specific Mortality With Tumor Size in Stage IVB Patients.

Purpose: To investigate the risk-stratifying utility of tumor size and a threshold for further stratification on cancer-specific mortality of thyroid cancer (TC) patients in stage IVB. Methods: One thousand three hundred and forty-five patients (620 males and 725 females) with initial distant metastasis over 55 years between 2004 and 2016 from Surveillance, Epidemiology, and End Results databases were investigated, with a median follow-up time of 23 months [interquartile range (IQR), 5-56 months] and a median age of 70 years (IQR, 63-77 years). TC-specific mortality rates were calculated under different classifications. Cox regressions were used to calculate hazard ratios (HRs) and Kaplan-Meier Analyses were conducted to investigate TC-specific survivals. Results: In the whole cohort, patients with tumors >4 cm had the highest TC-specific mortality (67.9%, 330/486), followed by tumor size >1 cm but ≤ 4 cm (43.08%, 190/441), and tumor size ≤ 1 cm (32.69%, 34/104). Kaplan-Meier curves showed the increased tumor size was associated with a statistically significant decrease in TC-specific survival (P < 0.001). Papillary thyroid cancer (PTC) patients with tumors >4 cm had significantly higher hazard ratios (HRs) of 2.84 (1.72-4.70) and 3.11 (1.84-5.26) after adjusting age, gender, race, and radiation treatment, compared with patients with tumors ≤ 1 cm (P < 0.001). The TC-specific mortalities and survivals were further investigated among more detailed subgroups divided by different tumor size, and a threshold of 3 cm could be observed (P < 0.005) for risk stratification. Conclusions: Mortality risk increased with tumor size in PTC patients in stage IVB. Our findings demonstrated the possibility of further stratification in IVB stage in current TNM staging system. Patients with tumor size over 3 cm had an excessively high risk of PTC-specific mortality, which may justify the necessity of more aggressive treatment for them.

Glucose-Lipid Metabolism in Obesity with Elevated Prolactin Levels and Alteration of Prolactin Levels After Laparoscopic Sleeve Gastrectomy.

PURPOSE: We investigated the differences in metabolism between obesity with or without increased prolactin (PRL) and the change in PRL after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients were divided into two groups: obesity with normal PRL (NP, n = 123) and high PRL (HP, n = 108). Glucose-lipid metabolism and inflammation were measured. A total of 115 patients with obesity (NP, n = 64; HP, n = 51) underwent LSG were recruited, and PRL was measured at 12 months after LSG. RESULTS: (1) Blood glucose (BG), total cholesterol (TCH), LDL, triglyceride, and TNF-α were lower in the HP than in the NP group in the cross-sectional study (all P < 0.05). (2) PRL was negatively associated with neck circumference, waist-to-hip ratio, systolic blood pressure, heart rate, basal metabolism rate (BMR), ALP, TCH, and LDL in all subjects. PRL levels were positively associated with weight, HC, and BMR in males but were negatively associated with ALT, AST, ALP, BG 30 min, BG 60 min, FFA, and TCH in females (all P < 0.05). (3) Regression analysis showed that PRL negatively correlated with ALP and LDL-C in the whole baseline (ß = - 0.051, P = 0.002; ß = - 1.372, P = 0.033). PRL was a negative factor for ALP in females and a positive factor for BMR2 in males (ß = - 0.099, P = 0.041; ß = 0.005, P = 0.006). (4) PRL decreased in the HP group and increased in the NP group at 12 months post-operation (all P < 0.05). Increased PRL was associated with a change in TCH in the NP group (P < 0.05). CONCLUSION: Increased PRL resulted in improved glucose-lipid metabolism and chronic low-grade inflammation. LSG led to increased PRL in NP and decreased PRL in HP. Improved lipid was associated with increased PRL in NP after surgery. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OCS-12002381.

Insulin-Like Growth Factor 1 Related to Chronic Low-Grade Inflammation in Patients with Obesity and Early Change of its Levels After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein (IGFBP) have an influence on metabolism. However, changes in metabolism after sleeve gastrectomy (SG) are not clearly known. This study investigated the change in IGFBP3 levels in obesity after bariatric surgery. METHODS: We evaluated 36 patients with obesity (14 males, aged 31.36 ± 7.06 years and 22 females, aged 32.55 ± 11.40 years) at baseline and 3 months after SG. Changes in their IGF1, IGFBP3, and IGF1/IGFBP3 ratios and glucose-lipid metabolic, inflammation, and oxidative stress parameters were measured. Enzyme-linked immunosorbent assay was used to measure their IGF1 and IGFBP3 levels. RESULTS: (1) IGFBP3 levels were negatively associated with waist circumference (WC) and waist-to-hip ratio (r = - 0.482, P = 0.043; r = - 0.503, P = 0.033); total IGF1 levels were negatively associated with body mass index and WC (r = - 0.569, P = 0.014; r = - 0.470, P = 0.048); and free IGF1 levels were negatively related to tumor necrosis factor (TNF)-α level independent of age (r = - 0.544, P = 0.020). Free IGF1 levels were negatively associated with uric acid, interleukin-6 (IL-6), IL-8, and TNF-α levels (r = - 0.646, P = 0.032; r = - 0.667, P = 0.025; r = - 0.641, P = 0.033; r = - 0.733, P = 0.010) and positively associated with superoxide dismutase activity (r = 0.635, P = 0.036) in females; this relation was not significant in males (all P > 0.05). Total IGF1 was also negatively associated with C-reactive protein (CRP) level in females (r = - 0.671, P = 0.024). (2) IGFBP3 level significantly decreased at 3 months after bariatric surgery in females (P < 0.001) but not in males (P = 0.815). Total IGF1 level significantly decreased after bariatric surgery (P = 0.048); the change was also significant in females (P = 0.014) but not in males (P = 0.626). Free IGF1 level after bariatric surgery was not statistically different between males (P = 0.605) and females (P = 0.628). (3) In females, the change in IGFBP3 level was associated with a change in high-density lipoprotein cholesterol and free fatty acid levels (r = 0.607, P = 0.003; r = 0.546, P = 0.016), and a change in total IGF1 level was associated with a change in CRP level (r = 0.664, P = 0.009). CONCLUSION: IGF1 level was related to chronic low-grade inflammation and oxidative stress in obesity, especially in females. IGFBP3 and IGF1 levels decreased in obesity after SG, especially in females. Changes in IGF/IGFBP3 levels were associated with a change in the inflammatory state after surgery.

The Association Between Lymph Node Stage and Clinical Prognosis in Thyroid Cancer.

Purpose: To investigate the association between lymph node (N) stage and clinical outcome in thyroid cancer patients with initial distant metastasis. Methods: A total of 3,198 cases (1,435 males and 1,763 females) between 2004 and 2015 with initial distant metastasis were obtained from the surveillance, epidemiology, and end results (SEER) database. Patients with a median follow up time of 13 months and a median age of 66 years were analyzed. A total of 1,407 cases had detailed information regarding the four most common metastatic organs after the year 2010. Kaplan-Meier (KM) analyses, log-rank tests, Cox regression, and logistic regression analyses were used. Results: Among the whole cohort, 33.4% (1,069/3,198), 14.5% (464/3,198), 10.1% (322/3,198), 34.2% (1,094/3,198), and 7.8% (249/3,198) of the patients were at the stage of N0, NX, N1a, N1b, and N1NOS (referring to metastasis to regional lymph nodes but not otherwise specified), respectively. The KM curves demonstrated that the patients at the NX stage had the worst survival. The NX and N1b groups had the highest hazard ratios (HRs) of 1.83 (95%CI 1.46-2.31) and 1.78 (95%CI 1.52-2.10) after adjusting age, race, gender, and tumor size (p < 0.001) compared with N0 group. The lung was the most common metastatic site, with a rate of 51.2% (720/1,407). Compared with the N0 group, N1 patients had higher odds (OR 1.63, 95%CI 1.31-2.01, p < 0.001) for lung metastasis. Similar results were obtained in papillary thyroid cancer (PTC) sub-cohort. Conclusions: Overall, the TC patients at the NX stage had the highest mortality risk, followed by N1b, N1a, and N0 groups. Compared with N0 patients, N1 patients were more likely to have lung metastasis. The poor prognosis for TC patients with the NX stage may make more aggressive treatment reasonable.

Changes of serum retinol-binding protein 4 associated with improved insulin resistance after laparoscopic sleeve gastrectomy in Chinese obese patients.

BACKGROUND: Serum retinol-binding protein 4 (RBP4) plays a critical role in insulin resistance. The mechanism behind the impact of laparoscopic sleeve gastrectomy (LSG) on glucose metabolism is unclear. Hence, we aimed to investigate the triangle relationship between the RBP4, glucose metabolism, and LSG in patients of Chinese ethnicity. METHODS: The study enrolled eighty-two obese patients. Glucose-lipid metabolic index, uric acid (UA), superoxide dismutase (SOD), free triiodothyronine (FT3), free thyroxin (FT4) and thyrotropin (TSH) were measured. RBP4 levels were detected by enzyme-link immunosorbent assay. 30 obese patients underwent LSG were studied. All these markers were measured again at a time interval of 3 and 6 months after surgery. RESULTS: (1) Circulating RBP4 levels were positively associated with body mass index(BMI), blood glucose in 0 min (BG0), BG30, BG120, BG180, fasting inulin(FINS), fasting C peptide(FCP), homeostasis model of assessment for insulin resistance index (HOMA-IR), SOD, TSH and negatively associated with Matsuda index in obesity with a significant difference (P < 0.05). RBP4 levels in the patients with impaired fasting glucose (IFG), insulin resistance or hyperinsulinemia were significantly higher than the patients without IFG, insulin resistance or hyperinsulinemia (P = 0.035, P = 0.001, and P = 0.007). (2) LSG resulted in significantly decreased FBG, FINS, FCP and HOMA-IR at 3, 6 months after surgery (all P < 0.05). The RBP4 levels were significantly decreased after surgery (all P < 0.05) with no gender difference. (3) The change in RBP4 levels was significantly associated with the change in FINS, FCP, HOMA-IR, and HOMA-ß at 6 months and the change in TSH at 3 months after surgery in males (all P < 0.05). The change in RBP4 levels were significantly associated with the change in FINS, FCP, HOMA-IR, HOMA-ß, and TCH at 3 months after surgery in females (all P < 0.05). CONCLUSIONS: Overall, our results interpret the significant correlations between RBP4, glucose-lipid metabolism, oxidative stress and thyroid function in obese patients. Further, the LSG brings a decline in RBP4 levels and that may contribute partly to the improved insulin resistance in obese Chinese patients.

Alteration of Bone Mineral Density Differs Between Genders in Obese Subjects After Laparoscopic Sleeve Gastrectomy: Bone Morphogenetic Protein 4 May Count.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) has proven to be successful in weight reduction but with potential loss of bone mass. Previous studies indicated that bone morphogenetic protein 4 (BMP4) plays an important role in both bone formation and glucose-lipid metabolism. This study aimed to investigate the changes in bone mineral density (BMD), bone metabolic parameters, and serum BMP4 levels in obese Chinese subjects after LSG. METHODS: Seventy-one obese patients (34 males, age 31.70 ± 9.61 years and 37 females, age 32.80 ± 11.45 years) were enrolled. BMD (at the right hip, femoral neck, and lumbar spine 1-4 (L1-L4)) was measured by dual-energy X-ray absorptiometry, bone metabolic markers, and routine anthropometric/laboratory biochemical parameters at baseline, 3, 6, and 12 months after LSG (abbreviated as 3, 6, and 12 M post-LSG, respectively) were recorded. Serum BMP4 levels were measured by enzyme-linked immunosorbent assay. RESULTS: LSG led to dramatic weight loss with improved glucose-lipid metabolism in all patients. In females, BMD was significantly decreased at the right hip at all time points studied and at the femoral neck at 6 and 12 M post-LSG (P < 0.05 or P < 0.01). In males, BMD was not significantly changed (all P > 0.05). Intriguingly, serum BMP4 levels were reduced slightly at 3 M post-LSG (P = 0.463) and were significantly at 6 M post-LSG (from 75.51 ± 16.54 to 65.40 ± 10.51 pg/mL, P = 0.048) in females, but unchanged in males (all P > 0.05). Vitamin D and 25-hydroxy vitamin D were increased in males at 12 M post-LSG (all P < 0.05). Osteocalcin was increased in males at all time points studied and in females at 3 and 6 M post-LSG (all P < 0.05). Type I collagen was increased in males at 3 and 6 M post-LSG and in females at all the time points studied (all P < 0.05). CONCLUSIONS: The effect of LSG on BMD differs between genders, decreasing significantly in females while remaining unchanged in males. Moreover, decreased BMP4 levels may partly account for the diminished BMD in obese Chinese female patients after LSG.