Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity.

Obesity is a complex metabolic disorder, manifesting as excessive accumulation of body fat. Ten-Eleven Translocation-2 (TET2) has garnered significant attention in the context of obesity due to its crucial role in epigenetic regulation and metabolic homeostasis. In this study, we aimed to investigate the effect of endothelial TET2 on obesity and explore the potential mechanism. We generated endothelial cell-specific TET2 deficiency mice and investigated endothelial TET2 using transcriptomic and epigenomic analyses. We determined the downregulation of endothelial TET2 in white adipose tissues. Furthermore, we identified that endothelial TET2 loss aggravated high-fat diet-induced obesity by inhibiting vascularization and thus suppressing white adipose tissue browning. Mechanistically, endothelial TET2 modulates obesity by engaging in endothelial fatty acid oxidation and angiocrine-mediated secretion of bone morphogenetic protein 4 (BMP4), in which nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a key mediator. Our study reveals that endothelial TET2 regulates white adipose tissue browning by interacting with NRF2 to facilitate fatty acid oxidation and lipolysis in adipocytes.

The causal effects of leisure screen time on irritable bowel syndrome risk from a Mendelian randomization study.

Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029-1.219) and weighted median (OR = 1.112, 95% CI 1.000-1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025-1.248) and weighted median (OR = 1.151, 95% CI 1.020-1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996-1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

OBJECTIVE: To explore insulin secretion patterns, ß-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). RESULTS: Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and ß-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

Association Between Abdominal Adipose Tissue Distribution and Obstructive Sleep Apnea in Chinese Obese Patients.

Purpose: Factors related to the occurrence of obstructive sleep apnea syndrome (OSAS) in obesity have not been fully clarified. The aim of this study was to identify the association between OSAS and abdominal fat distribution in a cohort of Chinese obese patients. Methods: This cross-sectional study collected demographic data of 122 obese patients who were admitted into the in-patient unit of the Department of Endocrinology, Shanghai Tenth People's Hospital from July 2018 to January 2021. OSAS was diagnosed based on the results of overnight polysomnography, and the abdominal fat distribution was measured by bioelectrical impedance analysis (BIA). Univariate and multivariate logistic regression analyses were used to investigate the association between OSAS and the distribution of abdominal fat. Results: (1) The mean age (SD) of the obese patients included was 32.44 (11.81) years old, and the overall incidence rate of OSAS was 51.06%. Twenty-four (25.53%) patients had mild OSAS, 10 (10.64%) had moderate OSAS, and 14 (14.89%) had severe OSAS. The apnea hypopnea index (AHI) of men was significantly higher than that of women (5.50, interquartile range (IQR) 3.80-30.6 vs. 4.2, IQR 1.4-12 events/h, p = 0.014). Meanwhile, men had a significantly higher visceral fat area when compared with women (180.29 ± 51.64 vs. 143.88 ± 53.42 cm2, p = 0.002). (2) Patients with OSAS had a significantly higher waist circumference, fasting plasma glucose, 2 h postprandial plasma glucose, glycated hemoglobin, and visceral fat area than patients without OSAS (all p < 0.05). (3) AHI was significantly positively associated with BMI, neck circumference, waist circumference, and visceral fat area (r = 0.306, p = 0.003; r = 0.380, p < 0.001; r = 0.328, p = 0.002; r = 0.420, p < 0.001) but not with subcutaneous fat area (p = 0.094). Multivariate analysis demonstrated that abdominal fat area and fasting plasma glucose were independent risk factors for OSAS (odds ratio, 1.016; 95% confidence interval, 1.005-1,026, p = 0.005; odds ratio, 1.618; 95% confidence interval, 1.149-2.278, p = 0.006). Conclusions: In obese patients, the abdominal visceral adipose deposit but not the subcutaneous fat area was associated with OSAS and was an independent risk factor for OSAS. Therefore, improving the distribution of abdominal fat may contribute to alleviating the severity of OSAS in obesity.

Effect of trimodal pre-rehabilitation on the rehabilitation of patients with gastrointestinal tumors in the perioperative period.

OBJECTIVE: To explore the effects of trimodal pre-rehabilitation on the rehabilitation of patients with gastrointestinal tumors in the perioperative period. METHODS: Clinical data of 878 patients with gastrointestinal tumors undergoing surgical treatment in our hospital were analyzed in this retrospective study. They were divided into a control group and an observation group. The patients in the control group received only routine preoperative education and guidance before operation, while those in the observation group received preoperative trimodal pre-rehabilitation. The nutritional status, sleep quality, psychological status, and physical function of two groups were compared 1 day before operation and at discharge. The postoperative complications, length of hospital stays, and hospitalization expenses were compared. The patients were followed up for three months after discharge from the hospital, and the quality of life between groups was compared. RESULTS: The nutritional status of two groups 1 day before operation and at discharge was improved compared with that at admission (all P<0.001). The nutritional status in the observation group was better than that in the control group 1 day before operation. The scores of sleep quality, psychological status, and physical function of the observation group were higher than those in the control group 1 day before surgery and at discharge (all P<0.001). The observation group had shorter hospital stays and lower hospitalization expenses than the control group (all P<0.001). The 3-month follow-up after discharge showed that the observation group had higher quality of life than the control group (all P<0.05). CONCLUSION: Trimodal pre-rehabilitation can improve the preoperative nutritional status, sleep quality, psychological state, and physical function of patients with gastrointestinal tumors during the perioperative period. Besides, it can shorten the hospital stays, reduce the total hospitalization expenses, and improve the quality of life of patients after discharge. It is worthy of clinical promotion.

Serum FABP1 Levels Correlate Positively with Obesity in Chinese Patients After Laparoscopic Sleeve Gastrectomy: a 12-Month Follow-up Study.

OBJECTIVE: The role of liver fatty acid-binding protein (FABP1) in obesity is presently unclear. We investigated the association of FABP1 with obesity and the changes noted after laparoscopic sleeve gastrectomy (LSG) in a Chinese population. METHODS: The cross-sectional analysis included 187 individuals: 65 had normal weight (18.5 ≤ body mass index (BMI) < 24 kg/m2), 59 were overweight (24 ≤ BMI < 28 kg/m2), and 63 were obese (BMI ≥ 28 kg/m2). We also assessed 25 severely obese patients (BMI, 38.58 ± 4.59 kg/m2) at baseline and at 3, 6, and 12 months after LSG to observe FABP1 levels. RESULTS: FABP1 levels in the obese (30.33 ± 23.59 ng/ml, **P < 0.01, ***P < 0.001) and overweight (18.96 ± 18.75 ng/ml, P = 0.471) individuals were significantly higher than those in normal weight individuals (14.30 ± 9.37 ng/ml). Linear regression analysis revealed that the FABP1 levels were positively correlated with BMI (R2 = 0.201, ***P < 0.001), ALT (R2 = 0.324, ***P < 0.001), AST (R2 = 0.387, ***P < 0.001), m-AST (R2 = 0.160, ***P < 0.001), γ-GT (R2 = 0.106, ***P < 0.001), DBil (R2 = 0.078, ***P < 0.001), UA (R2 = 0.111, ***P < 0.001), FBG (R2 = 0.066, ***P < 0.001), LDL (R2 = 0.042, **P = 0.005), and were negatively correlated with HDL (R2 = 0.051, **P = 0.002). After adjusting for age, sex, ALT, AST, TC, TG, HDL, LDL, FBG, and UA, FABP1 was independently correlated with BMI (*P < 0.05). With decreasing BMI after LSG, the FABP1 levels (29.46 ± 21.19 ng/ml, P = 0.463, P = 0.06, *P < 0.05) also decreased at 3 (23.00 ± 22.77 ng/ml), 6 (14.41 ± 15.48 ng/ml), and 12 months (11.55 ± 3.27 ng/ml). CONCLUSION: Serum FABP1 levels are closely correlated with obesity and many metabolic factors, and we found that with the decrease in BMI after LSG, the FABP1 levels also progressively decreased postoperatively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-OCS-12002381.

Reduction in Thyroid-Stimulating Hormone Correlated with Improved Inflammation Markers in Chinese Patients with Morbid Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. METHODS: Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. RESULTS: SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P < 0.001). TSH levels were declined significantly in both groups but were more pronounced in SH group (P < 0.001), whereas no change in FT4 in either group. Additionally, we observed marked reduction of IL-6, TNF-α, and CRP in SH group, as well as TNF-α and CRP in euthyroid group. After adjusting for age, baseline BMI, and changes in BMI, decrease in TSH correlated significantly with decreased HOMA-IR and TNF-α in euthyroid group and decreased fasting insulin (FINS), IL-6, TNF-α, and CRP in SH group. CONCLUSION: LSG promotes TSH reduction in patients with morbid obesity that is more pronounced in patients with SH and correlated with improved inflammatory state after surgery.

Alterations in Fat Mass and Bone Mineral Density Are Associated with Decreased Lipocalin-2 After Laparoscopic Sleeve Gastrectomy in Obese Chinese Women.

OBJECTIVE: Lipocalin-2 (LCN2) plays an important role in the regulation of the obesity and obesity-related dysmetabolic state. This study aimed to analyze serum LCN2 level in Chinese women with obesity before and after laparoscopic sleeve gastrectomy (LSG) and determine the association between alteration in fat mass and bone mineral density (BMD) and LCN2 level. METHODS: Fifty-two women (38 patients with obesity and 14 with normal body mass index (BMI)) were enrolled in this study. All patients with obesity underwent LSG. BMDs of the arm, leg, thoracic and lumbar spine, and pelvis were measured by dual-energy X-ray absorptiometry. Body fat mass and distribution were measured by dual-energy X-ray absorptiometry, and routine anthropometric/laboratory biochemical parameters at baseline and 3 and 12 months after LSG were recorded. Serum LCN2 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Serum LCN2 level was significantly higher in women with obesity than in the controls with normal BMI (102.70 ± 27.19 vs. 80.66 ± 19.55 ng/mL, P = 0.009). LCN2 level was decreased at 3 and 12 months after LSG (86.73 ± 26.79 ng/mL, P = 0.171, and 64.79 ± 28.39 ng/mL, P < 0.001, respectively). LSG led to marked body fat mass and slight BMD decrease. Decreased LCN2 level was significantly correlated with alterations in left and right leg BMDs and trunk fat mass at 12 months after LSG. CONCLUSIONS: Obesity was associated with up-regulated serum LCN2 level. Decreased LCN2 level was positively correlated with changes in BMD and fat mass at 12 months after LSG in Chinese women.

Sarcopenia is an effective prognostic indicator of postoperative outcomes in laparoscopic-assisted gastrectomy.

BACKGROUND: The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer. MATERIALS AND METHODS: We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications. RESULTS: The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309-4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274-5.944; P = 0.010) were independent risk factors for short-term postoperative complications. CONCLUSION: Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy.

Changes in inflammatory markers correlated with increased testosterone after laparoscopic sleeve gastrectomy in obese Chinese men with acanthosis nigricans.

Bariatric surgery is an effective method for severe obesity and its related comorbidities. This study was performed to explore the alterations of sex hormones and inflammatory markers following laparoscopic sleeve gastrectomy (LSG) among obese Chinese men with acanthosis nigricans (AN). Sixty-five obese men who underwent LSG were enrolled, comprising simple obesity without AN (OB group, n = 20) and obesity with AN (AN group, n = 45). There were 31 healthy male controls with normal body mass index (BMI) included. Anthropometry data, inflammatory markers, sex hormones and metabolic parameters were compared preoperatively and 12 months post-operatively. At baseline, patients in the AN group were associated with more severe metabolic abnormalities than the OB and control groups. Twelve months after surgery, AN patients obtained significant improvement in skin condition and reduction in AN score. BMI, fasting insulin (FINS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), tumor necrosis factor-α (TNF-α) and total testosterone (TT) were significantly changed in both groups, while interleukin (IL)-6, IL-8 and C-reactive protein were changed significantly only in the AN group. Moreover, FINS, HOMA-IR, TT and IL-6 levels were changed more in the AN group than those in the OB group. Multivariate regression analysis revealed that TT increase correlated significantly with reduction in FINS and HOMA-IR in both groups, but correlated with changes in IL-6 only in the AN group. In conclusion, LSG is effective in improving the skin condition of obese men with AN. The increased TT in AN patients correlated with amelioration of inflammatory state in addition to insulin resistance after LSG.

O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT.

Emerging studies have revealed that O-GlcNAcylation plays pivotal roles in the tumorigenesis of colorectal cancers (CRCs). However, the underlying mechanism still remains largely unknown. Here, we demonstrated that Yin Yang 1 (YY1) was O-GlcNAcylated by O-GlcNAc transferase (OGT) and O-GlcNAcylation of YY1 could increase the protein expression by enhancing its stability. O-GlcNAcylation facilitated transformative phenotypes of CRC cell in a YY1-dependent manner. Also, O-GlcNAcylation stimulates YY1-dependent transcriptional activity. Besides, we also identified the oncoproteins, SLC22A15 and AANAT, which were regulated by YY1 directly, are responsible for the YY1 stimulated tumorigenesis. Furthermore, we identified the main putative O-GlcNAc site of YY1 at Thr236, and mutating of this site decreased the pro-tumorigenic capacities of YY1. We concluded that O-GlcNAcylation of YY1 stimulates tumorigenesis in CRC cells by targeting SLC22A15 and AANAT, suggesting that YY1 O-GlcNAcylation might be a potential effective therapeutic target for treating CRC.

Effects of CO2 pneumoperitoneum on proliferation, apoptosis, and migration of gastrointestinal stromal tumor cells.

BACKGROUND: The purpose of the study was to investigate the proliferation and migration capability of human gastrointestinal stromal tumor line GIST-T1 after exposure to different pressures and times of CO2 pneumoperitoneum. METHODS: We established simulated CO2 pneumoperitoneum environment in vitro and divided the human GIST cell GIST-T1 into open control group, 8 mmHg CO2 pneumoperitoneum treatment group and 15 mmHg CO2 pneumoperitoneum treatment group. Each group was divided into two subgroups respectively cultured for 1 h and 3 h. pH value of cell culture, cell growth curve, and cell cycle distribution of each group was measured. By application of scratch healing tests and Transwell chamber experiments, mobility ratio and number of cells through 8 µm membranes were measured to assess the migration ability of cells in each group after intervention. RESULTS: Cell culture pH value of each subgroup in CO2 group decreased significantly after exposed in CO2 pneumoperitoneum (P < 0.01). The proliferation of GIST-T1 cells in 15 mmHg CO2 group was significantly inhibited early (1-2 days) (P < 0.05) and the proliferation of GIST-T1 cells in 8 mmHg CO2 1 h subgroup and 15 mmHg CO2 1 h subgroup was increased significantly late (4-6 days) (P < 0.05) after the interventions of CO2 pneumoperitoneum. The percentage of cells in G0-G1 phase increased, the percentage of S phase cells decreased (P < 0.01) in 1-h subgroup and 3-h subgroup of 15 mmHg CO2 group 24 h after exposure to CO2. The percentage of cells in S phase increased in 1-h subgroup of 8 mmHg CO2 group and decreased in 3-h subgroup of 15 mmHg CO2 group 72 h after exposure to CO2. In the Transwell chamber experiment, the cell number through 8-µm membrane increased significantly (P < 0.01) in 3-h subgroup of CO2 group compared to that in 3-h subgroup of control group. CONCLUSIONS: The routine pressure and duration of CO2 pneumoperitoneum used in clinic did not promote the proliferation of gastrointestinal stromal tumors, but had a potential risk of increasing postoperative recurrence and distant metastasis.

Clinical Application of Enhanced Recovery After Surgery in Perioperative Period of Laparoscopic Colorectal Cancer Surgery.

OBJECTIVE: To investigate the clinical application value of enhanced recovery after surgery (ERAS) combined with the laparoscopic technique in the radical resection of colorectal cancer. METHODS: A total of 200 patients undergoing laparoscopic radical surgery for colorectal cancer from June 2014 to June 2017 were selected and randomly divided into ERAS group (n = 100) and conventional (CON) group (n = 100). The ERAS group adopted enhanced recovery approach after surgery for perioperative treatment, while the CON group adopted a CON approach. The operation time, blood loss, first exhaust time, first defecation time, extubation time, complication rate (incision infection, pneumonia, gastric retention, anastomotic leakage, intestinal obstruction, etc.), scores of visual analog scale (VAS) 1, 3, and 7 days after surgery, and nutritional status (albumin, total protein) 1, 3, and 7 days after surgery were compared and analyzed. RESULTS: Compared with the CON group, the ERAS group had significantly shorter first exhaust time, first defecation time, and extubation time (all P < .05). The incidence of overall complications in the ERAS group was less than those in the CON group (P < .05); and albumin and total protein were significantly higher in the ERAS group than in the CON group (both P < .05). CONCLUSIONS: ERAS combined with laparoscopic techniques for the treatment of colorectal cancer is a safe and feasible practice. It not only promoted the recovery of gastrointestinal function but also improved the perioperative nutritional status of patients.

Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity-related diabetes.

BACKGROUND AND OBJECTIVE: The stomach plays an important role in obesity and obesity-related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. METHODS: We performed gene microarray and real time-polymerase chain reaction (RT-PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. RESULTS: In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co-regulated in both comparisons. Seven differentially expressed genes were validated by RT-PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G-protein coupled receptor biological processes, and primarily participated in the PI3K-Akt and AGE-RAGE signaling pathways. CONCLUSIONS: Obesity and obesity-related diabetes are associated with important gene expression and pathway alterations in the stomach.

Changes in Sex Hormones After Laparoscopic Sleeve Gastrectomy in Chinese Obese Men: a 12-Month Follow-Up.

BACKGROUND: To examine changes in sex hormones after laparoscopic sleeve gastrectomy (LSG) in Chinese obese male patients and their correlation with metabolic parameters including serum uric acid (SUA) METHODS: A total of 56 obese men with body mass index (BMI) 41.9 ± 5.8 kg/m2 undergoing LSG were selected. Thirty-one healthy men with normal BMI were included as controls. Levels of total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), SUA, and other metabolic indices were compared pre- and 12 months post-LSG. Calculated free testosterone (cFT) was calculated from TT and SHBG using an empirical equation. RESULTS: At baseline, low TT and hyperuricemia (HUA) were common in obese men. Twelve months after LSG, statistically significant reduction in weight, BMI, and glucolipid metabolism indices was noted. SUA levels declined remarkably from 474.9 ± 94.6 to 338.8 ± 81.9 µmol/L and the percentage of HUA decreased from 76.8 to 54.1% (all P < 0.001). Additionally, significant increases in TT, SHBG, and cFT as well as a decrease in percentage of low TT were observed after LSG (all P < 0.05), while E2, FSH, and LH did not change significantly. Moreover, changes in TT levels were more pronounced than those of other sex hormones. After age and BMI were adjusted, increased TT levels were correlated significantly with decreased SUA (ß = - 1.077, P < 0.05), BMI (ß = - 0.712, P < 0.001), and HOMA-IR (ß = - 0.652, P < 0.05), as well as increased SHBG (ß = 0.759, P < 0.001). CONCLUSIONS: LSG promotes a significant increase in TT levels in Chinese obese men, which may be mediated by substantial weight loss, SUA reduction, and improved insulin resistance (IR).

Long Noncoding RNA BCYRN1 Promotes the Proliferation of Colorectal Cancer Cells via Up-Regulating NPR3 Expression.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) constitute a large proportion of noncoding transcripts that have recently emerged as a new class of important regulators in cancers. LncRNA BCYRN1, also known as BC200, has a potential function in tumorigenesis. However, the clinical significance of BCYRN1 and its effect on colorectal cancer (CRC) progression remains unclear. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of BCYRN1 in CRC tissues and cell lines. The biological function of BCYRN1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. Microarray bioinformatics analysis was performed to analyze the putative targets of BCYRN1. RESULTS: The results showed that BCYRN1 expression was significantly upregulated in 96 CRC tumor tissues compared with para-carcinoma control tissues. Additionally, BCYRN1 overexpression was associated with larger tumor size and advanced pathological stages in CRC patients. In vitro BCYRN1 knockdown significantly inhibited the proliferation and apoptosis of CRC cells. Furthermore, NPR3 was identified to be a target of BCYRN1 and was downregulated by BCYRN1 knockdown. CONCLUSION: Together, we provide the first evidence that BCYRN1 plays an oncogenic role in CRC cells. BCYRN1 may be a promising prognostic biomarker and a potential therapeutic target for CRC.

UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p.

Long noncoding RNAs (lncRNAs) have emerged as regulators in a variety of biological processes, including carcinogenesis in human cancer. UCA1 has been reported to be upregulated in gastric cancer (GC); however, the underlying functional roles of UCA1 in GC have not been established. In the current study, we showed that UCA1 is significantly higher in GC tissues and cells compared with adjacent normal tissues and a gastric epithelium cell line, respectively. Higher UCA1 expression was associated with lymph node metastasis, TNM stage, and poor overall survival (OS) in GC patients. In vitro functional studies confirmed that UCA1 promotes cell proliferation, colony formation ability, and cell invasion in GC cells. We demonstrated that knockdown of UCA1 inhibits tumor growth in vivo. The double luciferase reporter, RNA-binding protein immunoprecipitation assay, and RNA pull down assay demonstrated that miR-590-3p serves as a target for UCA1. UCA1 promoted cell proliferation and invasion by negatively regulating miR-590-3p expression. Moreover, we demonstrated that CREB1 is a downstream target of miR-590-3p and UCA1 activates CREB1 expression by sponging to miR-590-3p. Thus, these results showed that UCA1 functions as an oncogene in GC and may be a target for treatment of GC.

Laparoscopic sleeve gastrectomy improves body composition and alleviates insulin resistance in obesity related acanthosis nigricans.

BACKGROUND: Acanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans. METHODS: A total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis. RESULTS: Patients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P < 0.001).Alleviated insulin resistance and more trunk fat loss than limbs' were observed in both groups (P value < 0.01). In AN group, preoperative android fat mass (FM) was positively correlated with fasting insulin and natural logarithm of HOMA-IR (LNIR) (r = 0.622, 0.608, respectively; all P < 0.01). Besides, changes in android FM and visceral adipose tissue (VAT) also showed significantly positive correlation with changes in LNIR (r = 0.588, r = 0.598, respectively; all P < 0.01). CONCLUSIONS: LSG had a positive impact on body composition and skin condition in Chinese obese patients with AN. Loss of android FM and VAT might result in the alleviation of insulin resistance in AN patients. Android fat distribution seems to be a potential indicator of postoperative metabolic benefits for obese patients with AN.

[Effect of laparoscopic sleeve gastrectomy on sex hormone in male severe obesity].

OBJECTIVE: To investigate the effect of laparoscopic sleeve gastrectomy(LSG) on sex hormone in male patients with severe obesity. METHODS: Retrospective analysis was performed in 31 male patient with severe obese [body mass index(BMI) ≥28 kg/m2, obesity group] who underwent LSG in Shanghai Tenth People's Hospital of Tongji University from December 2012 to May 2016. The anthropometric parameters(weight, BMI, waist circumference, hip circumference, waist-hip ratio, body fat percentage), glucose metabolic indices [fasting plasma glucose(FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance index(HOMA-IR)], and sex hormone parameters [estradiol(E2), total testosterone (TT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were collected preoperatively and 1, 3, 6 months postoperatively. In addition, 31 healthy male volunteers with normal BMI were consecutively recruited in this study as control group. The above-mentioned parameters were also determined in control group. Changes of these variables before and after surgery were analyzed. Pearson method was used to analyze the correlation of TT with anthropometric parameters and glucose metabolic indices before and after surgery. RESULTS: The average age of patients in obesity and control group was (32.9±9.7) (18 to 56) years and (30.7±8.9) (18 to 49) years. Compared to the control group, obesity group had significantly higher anthropometric parameters and glucose metabolic indices before surgery (all P<0.05). In obesity group, the anthropometric and glucose metabolic indices significantly decreased at 1 to 6 months after surgery compared to those before surgery (all P<0.05). At 1 month after surgery, the anthropometric parameters and glucose metabolic indices in obesity group were significantly higher than those in control group (all P<0.05). At 3, and 6 months after surgery, there were no significant differences in glucose metabolic indices between obesity and control group (all P>0.05), while the anthropometric parameters in obesity group were still significantly higher than those in control group(all P<0.05). The sex hormone parameters in control and obesity group before surgery were as follows: E2: (100.2±23.5) pmol/L and (129.2±81.9) pmol/L; TT: (18.0±4.9) nmol/L and (8.4±4.5) nmol/L; FSH: (4.5±3.1) IU/L and (4.3±2.5) IU/L; LH: (4.4±1.7) IU/L and (5.3±2.6) IU/L. Compared to control group, the TT level of obese patients before surgery significantly decreased(P=0.000), while no significant differences were observed in the levels of E2, FSH, and LH(all P>0.05). The TT levels were significantly increased at 1, 3, 6 months after surgery[(13.1±7.0), (13.6±5.7), (21.0±19.3) nmol/L, respectively, all P<0.05] and the E2 level was significantly decreased at 6 months after surgery [(91.4±44.9) pmol/L, P<0.05], while no significant differences were observed at 1 and 3 months after surgery (all P>0.05). Furthermore, the FSH and LH levels did not exhibit significant change at 1, 3, and 6 months after surgery compared to those before surgery (all P>0.05). At 1 month after surgery, no significant correlations were examined in the change value of TT levels (▹TT) with the changes of BMI(▹BMI), FPG(▹FPG), FINS(▹FINS), HOMA-IR(▹HOMA-IR), and E2(▹E2) (all P>0.05). At 3 months after surgery, ▹TT was negatively correlated with ▹BMI (r=-0.441, P=0.015), ▹FINS (r=-0.375, P=0.041), and ▹HOMA-IR(r=-0.397, P=0.030), but not correlated with ▹FPG and ▹E2 (all P>0.05). At 6 months after surgery, ▹TT was negatively correlated with ▹BMI(r=-0.510, P=0.018) and ▹HOMA-IR (r=-0.435, P=0.049), but not correlated with ▹FPG, ▹FINS and ▹E2 (all P>0.05). CONCLUSIONS: Male severe obese patients are accompanied with abnormal sex hormone levels. LSG has a significant effect on weight loss and blood glucose improvement, and may ameliorate the sex hormone unbalance by improving the insulin resistance in men with severe obesity.