Anton Kui Sing Cheng

Circulating and visceral adipose miR-100 is down-regulated in patients with obesity and Type 2 diabetes.

Obesity is a major public health problem conferring substantial excess risk for Type 2 diabetes (T2D). The role of microRNAs (miRNAs) in obesity and adipose tissue is not clearly defined. We hypothesize that circulating miRNA expression profiles vary according to differences in body mass index (BMI) and T2D and circulating miRNAs may reflect adipose tissue expression. Compared to healthy, lean individuals, circulating miR-100 was significantly lower in obese normoglycemic subjects and subjects with T2D. In visceral adipose tissue, expression of miR-100 was lower from obese subjects with T2D compared to obese subjects without T2D. miR-100 expression was significantly lower after adipogenic induction in human visceral, subcutaneous adipocytes and 3T3-L1 adipocytes. miR-100 reduced expression of mammalian target of rapamycin (mTOR) and Insulin Growth Factor Receptor (IGFR) directly. Differentiation of 3T3-L1 was accelerated by inhibition of miR-100 and reduced by miR-100 mimic transfection. Our data provide the first evidence of an association of circulating miR-100 with obesity and diabetes. Additionally, our in-vitro findings, and the miR-100 expression patterns in site-specific adipose tissue suggest miR-100 to modulate IGFR, mTOR and mediate adipogenesis.

Acetyl-keto-β-boswellic acid induces lipolysis in mature adipocytes.

Recently, it was reported that naturally occurring pentacyclic triterpenoids such as ursolic acid have anti-adiposity property. We studied if acetyl-keto-β-boswellic acid (AKBA), an established anti-inflammation and anti-cancer pentacyclic triterpenoid which has similar chemical structure to ursolic acid, may modulate adipocyte phenotype. 3T3-L1 murine adipocytes and human subcutaneous adipocytes were treated with AKBA in different concentrations in vitro. AKBA triggered significant lipolysis in 3T3-L1 adipocytes as shown by reduced neutral lipids in cytosol and increased free fatty acids in culture medium. Increased lipolysis by AKBA was accompanied by up-regulation of lipolytic enzymes, adipocyte triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), and a decreased expression of lipid droplet stability regulator perilipin. In addition, AKBA treatment reduced phenotypic markers of mature adipocyte aP2, adiponectin and glut-4 in mature adipocytes. Further studies revealed that AKBA down-regulated PPAR-γ and C/EBP-α expression in a dose and temporal dependent manner in mature adipocytes. In human adipocytes, AKBA likewise mobilized lipolysis accompanied by down-regulation of PPAR-γ2 expression and loss of phenotypic markers of mature adipocytes.

Early outcomes of laparoscopic sleeve gastrectomy in a multiethnic Asian cohort.

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric operation worldwide. OBJECTIVES To report early outcomes of patients with LSG performed. SETTINGS University hospital and a restructured hospital, Singapore. METHODS Data of patients who underwent LSG as a primary procedure from 2008 to 2013 were analyzed for change in body mass index (BMI), percentage of weight loss (%WL), and percentage of excess weight loss (%EWL). The remission of obesity-related co-morbidities after LSG was analyzed. Logistic regression analyses were performed to determine predictive factors for perioperative complication and suboptimal EWL. RESULTS Two hundred operations were performed on a cohort that consisted of 74 Chinese, 57 Malay, and 52 Indian patients and 17 patients from other ethnic groups. Mean preoperative weight and BMI were 118.1±26.8 kg and 43.0±8.0 kg/m(2), respectively. Mean follow-up duration was 16.7±9.4 months. At 6, 12, 24 and 36 months, the percentage of patients followed-up were 79.5%, 75.7%, 50.0%, and 50.0%, and the mean %EWL were 51.2%, 61.2%, 60.9%, and 51.0%, respectively. Postoperative complications occurred in 9 patients (4.5%), 5 of whom (2.5%) required reoperation. There was no mortality in our series. Remission of type 2 diabetes mellitus (T2DM) was significantly associated with achieving>50% EWL (P = .009). Patients>50 years of age and higher preoperative BMI were significant factors for failure to achieve>50% EWL at 1 year after LSG. CONCLUSION LSG is a safe and effective operation for achieving significant weight loss and improvement of co-morbidities in multiethnic Asian population. Adequate EWL is important to achieve remission of T2DM. Older patients and higher preoperative BMI are predictive factors for suboptimal EWL.

Adiponectin Gene Polymorphisms and Type 2 Diabetes among Singaporean Chinese Adults

Background: Adiponectin is the most abundant circulating adipokine in human that regulates insulin actions. Association of adiponectin gene variations with type 2 diabetes (T2DM) has been reported albeit predominantly in non-Asian populations. Additionally, proof of variant functionality beyond statistical association is often unavailable. We studied six common (minor allele frequency ≥0.05) adiponectin single nucleotide polymorphisms (SNPs) in Singaporean Chinese adults with follow-up functional genetic experiments. Methods: In a case-control study (N=588), genotyping of six common adiponectin haplotype tagging SNPs [-3964A>G(rs822396), +45T>G(rs2241766), 276C>A(rs1501299), 973G>A(rs3774262), 4551G>C(rs1063539) and 5852G>A(rs6444175)] was performed using Taqman genotyping assay. Allele-dependent differential efficiency of mRNA expression was tested with quantitative real time PCR using human subcutaneous and omental adipose tissues. Results: Distributions of genotypes for all SNPs among controls were consistent with Hardy-Weinberg Equilibrium. Single locus, genotyped-based analysis suggested borderline significant ( P=0.07) association between an exon2 coding-synonymous +45T>G(rs2241766) and T2DM. We demonstrated that the relative mRNA expression of adiponectin gene was ~80% lower among carriers of minor G allele in human subcutaneous adipose tissue (N=43, p G(rs2241766) and T2DM among Singaporean Chinese adults. Functional experiments in both human subcutaneous and omental adipose tissue suggested that polymorphisms in +45T>G(rs2241766) may be associated with differential allelic expression.

Goal-directed program after sleeve gastrectomy improves weight loss.

BACKGROUND The aim of our study is to determine if a goal-directed program improves weight loss after sleeve gastrectomy. METHODS Our goal-directed program involves setting excess weight loss targets at fixed intervals after sleeve gastrectomy. We identified patients in 3 bariatric centers between April 2010 and July 2013 and compared the center that has a goal-directed weight loss program (goal-directed program) with the other 2 centers (standard program). RESULTS A total of 211 patients were included, with 129 patients in the goal-directed weight loss program. The 2 groups were similar in terms of gender distribution, ethnicity distribution, age, and preoperative weight, preoperative body mass index, and surgical technique. The follow-up rates at 3, 6, 9, and 12 months for patients in the goal-directed program was 84.5%, 75.2%, 59.7%, and 82.2%, respectively, compared with 65.9%, 68.3%, 51.2%, and 68.3% for the standard program. The percentage total weight loss at 3, 6, 9, and 12 months was 17.1%, 23.3%, 26.8%, and 28.6%, respectively, for the goal-directed program, compared with 15.3%, 21.8%, 24.4%, and 25.4%, respectively, for the standard program. The mean excess weight loss at 3, 6, 9, and 12 months were 40%, 54%, 62%, and 67%, respectively, for the goal-directed program group, and 36%, 50%, 54%, and 55%, respectively, for the standard program, where statistical significance (P<.005) was achieved at 12 months. CONCLUSION Our results suggest that a goal-directed protocol may improve weight loss outcomes after laparoscopic sleeve gastrectomy.

Step-up approach and video assisted retroperitoneal debridement in infected necrotizing pancreatitis: A case complicated by retroperitoneal bleeding and colonic fistula.

Introduction Infected Necrotizing Pancreatitis carries a high mortality and necessitates intervention to achieve sepsis control. The surgical strategy for proven infected necrosis has evolved, with abandonment of open necrosectomy to a step-up approach consisting of percutaneous drains and Video-assisted retroperitoneal debridement (VARD). We present a case that underwent VARD complicated by bleeding and colonic perforation and describe its management. Presentation of case A 38 year-old male with acute pancreatitis developed infected necrotizing pancreatitis. Initial treatment was by percutaneous drainage under radiological guidance and intravenous antibiotics. The infected retroperitoneal necrosis was then debrided using gasless laparoscopy through a mini-incision. Post-operatively, he developed peripancreatic bleeding which was controlled with angioembolisation. He also developed a descending colon fistula which was treated with laparotomy and defunctioning loop ileostomy. He recovered and subsequently had his ileostomy closed twelve months later. The colonic fistula recurred and was treated with endoscopic clips and histoacryl glue injection and finally closed. Discussion Step-up approach consists of the 3 Ds: Delay, drain and debride. VARD is recommended as it is replicable in general surgical units using standard laparoscopic instruments. Bleeding and colon perforation are potential complications which must have multi-disciplinary input, aggressive resuscitation and timely radiologic intervention. Defunctioning ileostomy is recommended to control sepsis in colonic fistulation. Novel fistula closing methods using endoscopic clips and histoacryl glue are potential treatment options. Conclusion Step-up approach and VARD is the new paradigm to treat necrotizing pancreatitis. Complications of bleeding and colon fistula are uncommon and require multi-disciplinary management.

Association of circulating proinflammatory marker, leucine-rich-α2-glycoprotein (LRG1), following metabolic/bariatric surgery

Obesity confers substantial excess risk for morbidity and mortality, especially for type 2 diabetes (T2D). Leucine‐rich‐α2‐glycoprotein 1 (LRG1), a novel proinflammatory factor, was recently reported to be higher in patients with T2D with complications of peripheral arterial disease. Association of LRG1, obesity, and weight loss is unknown. We examined whether plasma LRG1 is associated with obesity in health screening participants and if it predicts future weight loss in morbidly obese patients after metabolic/bariatric surgery.