Serum microRNA panels predict bariatric surgery outcomes.

OBJECTIVE: The weight losses after bariatric surgery are modulated by multiple factors in people with obesity. MicroRNAs (miRNAs) have been reported to show significant regulatory roles in adipose tissue. However, a serum miRNA signature to serve as a biomarker of sustained weight losses following bariatric surgery has not yet been established. METHODS: MiRNA microarray was used to identify differentially expressed miRNAs in the serum of patients with an effective response after bariatric surgery compared with those without. Excess weight loss > 55% at 6 months after surgery was defined as an effective response. RESULTS: Three miRNAs were shown to have a significantly differential expression between patients with or without an effective response following bariatric surgery. The miR-31-5p was downregulated, whereas miR-328-3p and miR-181a-5p were upregulated in the patients with effective responses compared with those without effective responses. Panels of the serum ratios of miR-328-3p/miR-31-5p or miR-181a-5p/miR-31-5p and individual BMI value exhibited good performance in preoperative prediction of treatment effectiveness. Bioinformatic analysis depicted that predicted targets of these miRNAs were involved in the regulation of the AMP-activated protein kinase signaling pathway. CONCLUSIONS: A circulating miRNA signature with clinical variables (BMI) can be a clinical biomarker to predict effectiveness following bariatric surgery.

FTO variants are associated with ANGPTL4 abundances and correlated with body weight reduction after bariatric surgery.

BACKGROUND: The FTO (fat mass- and obesity-associated) gene variant is an established obesity-susceptibility locus. FTO protein is a nucleic acid demethylase and FTO genetic variants form long-range functional connections with IRX3, which regulates fat mass and metabolism in humans. From our previous results, we found FTO regulates the metabolism of triglyceride in adipocytes through demethylating Angptl4 (angiopoietin-like protein 4) mRNA in mice. We hypothesized that the FTO genetic variants regulate ANGPTL4 abundances in human adipose tissues and affect the outcome after bariatric surgery. METHODS AND RESULTS: We recruited 188 obesity subjects with body mass indices (BMI)>35kg/m2 and 102 non-obese subjects with BMI<30kg/m2 from the OCEAN registry between 2011 and 2014. The distribution of FTO variants rs9939609 among participates was 73.79% TT, 23.79% AT, and 2.41% AA. The subjects with FTO variants AA or AT were correlated with higher BMI than those with FTO variants TT. The serum ANGPTL4 levels were significantly higher in obese subjects and positively correlated with the presence of FTO AA or AT haplotype. Of these participates, 84 obese subjects underwent bariatric surgery and adipose Angptl4 expressions were analyzed. The adipose Angptl4 mRNA levels and protein abundances were correlated with FTO AA or AT haplotype. The magnitude of excess body weight reduction 2 years after bariatric surgery was correlated with the adipose ANGPTL4 protein levels. CONCLUSION: Adipose ANGPTL4 abundances were affected by the presence of FTO obesity risk haplotype and correlated with excess weight loss percentage after bariatric surgery. These data signify the critical role of FTO variants and adipose ANGPTL4 in fatty acid metabolism and bariatric outcomes in humans.

Serum asprosin levels and bariatric surgery outcomes in obese adults.

BACKGROUND/OBJECTIVES: Asprosin is a novel fasting-induced glucogenic and orexigenic protein hormone. The clinical function of asprosin in obesity is currently unknown. This study investigated the association between asprosin abundance and the outcome of bariatric surgery. SUBJECTS/METHODS: Patients with body mass index more than 35 kg/m2 were recruited for the Obesity and Clock for Elegant Aging Registry in 2011-2016. Body weight changes, blood sugar, and asprosin were assessed in 117 patients receiving bariatric surgery and 57 non-obese subjects as normal control. Primary outcomes of excess weight loss percentage at 6 months after bariatric surgery were determined at follow-up. RESULTS: Asprosin levels were significantly higher in obese patients than in non-obese subjects (2360 ± 5094 vs. 307 ± 832 ng/ml, p < 0.0001). Multivariate analyses showed a significant association of asprosin abundance with excess body weight loss percentage at 6 months after surgery (p < 0.0001). After adjusted for age, sex, smoking, HbA1c, cholesterol, and triglyceride, serum asprosin level was the only independent predictor of 6 months excess weight loss percentage after bariatric surgery. Asprosin levels decreased significantly 6 months after bariatric surgery (162.2 ± 169.1 ng/ml). Furthermore, there was no association between asprosin and serum glucose levels in our study. CONCLUSION: This study provides novel evidence that higher asprosin concentrations before bariatric surgery were associated with the weight reduction magnitude at 6 months after surgery. Further studies are warranted to investigate whether asprosin has direct functions to modulate body weight regulation in humans after bariatric surgery.

MiR-122 marks the differences between subcutaneous and visceral adipose tissues and associates with the outcome of bariatric surgery.

The physiological roles and clinical impacts of the differences between visceral fat (VF) and subcutaneous fat (SF) are unclear. The present study aimed to compare the miRNA signatures between visceral fat (VF) and subcutaneous fat (SF) and study their influences on outcomes of bariatric surgery. To study the microRNA signatures of the VF and SF in obesity, we performed paired microRNA arrays of the adipose tissues from 20 bariatric surgery patients. The microRNA analysis identified miR-122 as the most significant signature between VF and SF. The tissue distribution, functions, and influences on adipogensis of miR-122 were analysed by Northern blotting, microRNA mimics and inhibitors, and whole-genome microarray analysis. The outcomes of body weight changes after bariatric surgery were analysed and correlated with the miR-122 abundances. Northern blotting confirmed that miR-122 was highly expressed in VF and SF. Bioinformatics analysis of the microarray revealed that proliferator activator receptor-γ (PPAR-γ) signalling was critically affected by miR-122. The modulation of PPAR-γ by miR-122 was confirmed in murine adipocytes and human adipose tissues. Furthermore, the differentiation of preadipocytes was significantly influenced by miR-122. In obese patients receiving bariatric surgery, the ratio of VF and SF miR-122 abundance correlated with 6-month and 1-year % excess body weight loss. Our findings indicate that miR-122 is highly expressed in adipose tissue. The abundance of miR-122 affects PPAR-γ signalling and adipocytes differentiation in vitro and human adipose tissues. Higher miR-122 in VF may be associated with greater body weight loss after bariatric surgery.

Laparoscopically assisted bowel surgery in an era of double-balloon enteroscopy: from inside to outside.

BACKGROUND: This report describes an integrated therapeutic method of double-balloon enteroscopy (DBE) and laparoscopically assisted bowel surgery (LABS) for small bowel diseases. METHODS: In this study, 34 patients with obscure gastrointestinal bleeding (OGIB, n=25) and abdominal pain (n=9) who underwent DBE and LABS were analyzed. Demographics, patient characteristics, diagnostic tests, DBE and LABS findings, surgical results, and long-term outcome were reviewed. RESULTS: All 34 patients underwent DBE without significant complications. Biopsy was performed for 16 patients, ink mark for 25 patients, and temporary homeostasis during DBE for 5 patients. Laparoscopically assisted bowel resection was performed for 27 patients, converted laparotomy for 6 patients, and laparoscopic diagnosis alone for 1 patient. The pathologic diagnoses included gastrointestinal stromal tumor (GIST) for eight patients, primary adenocarcinoma for three patients, lymphoma for three patients, Meckel's diverticulum for three patients, angiodysplasia for three patients, ulcer for two patients, lipoma for four patients, metastasis for three patients, jejunal diverticulosis for two patients, and tuberculosis ileitis, ileal varix, and lymphangioma for one patient each. No surgical mortalities or significant morbidities were noted. After a follow-up period of 14+/-3 months, 29 patients were well without disease recurrence. Two patients had symptomatic recurrence, and three patients died of cancerous progression. CONCLUSIONS: The combination of DBE and LABS represents an ideal therapeutic method, especially for OGIB caused by small bleeding neoplasms or vascular lesions.