Background: Bariatric surgery (BS) currently is the most effective treatment for severe obesity. To our knowledge, no data comparing different bariatric procedures regarding differences in gastrointestinal symptoms have been published.Methods: For this multicenter, prospective, nonrandomized clinical trial in Germany, 310 patients underwent screening, and 124 patients completed the study. Patients completed the following standardized questionnaires preoperatively and at 6 and 12 months after surgery: Gastrointestinal quality of life index, bowel disease questionnaire, and Cleveland clinic incontinence score.Results: Mean patient age was 44.4 years. Mean body mass index prior to surgery was 45.1 kg/m2. Physical function improved significantly after surgery (31.9 vs. 62.1 and 62.3, respectively, p < 0.001). Nausea and diarrhea symptoms worsened 12 months after sleeve gastrectomy (SG; p = 0.025 and p = 0.017, respectively). Constipation improved 12 months after SG (p = 0.006). Multivariate analysis revealed SG as an independent predictive factor for diarrhea (p = 0.026). Physical and emotional function improved for Roux-en-Y gastric bypass and SG.Conclusion: This study highlights differences in symptom outcomes after different bariatric procedures. Significant changes in bowel habits were seen especially after SG. Overall, BS improves quality of life. Side effects of surgery should not be a contraindication for surgery. However, patients can be educated regarding possible side effects, and the surgical procedure can be chosen individually.

Introduction Revisional bariatric surgery (RBS) for insufficient weight loss/weight regain or metabolic relapse is increasing worldwide. There is currently no large multinational, prospective data on 30-day morbidity and mortality of RBS. In this study, we aimed to evaluate the 30-day morbidity and mortality of RBS at participating centres. Methods An international steering group was formed to oversee the study. The steering group members invited bariatric surgeons worldwide to participate in this study. Ethical approval was obtained at the lead centre. Data were collected prospectively on all consecutive RBS patients operated between 15th May 2021 to 31st December 2021. Revisions for complications were excluded. Results A total of 65 global centres submitted data on 750 patients. Sleeve gastrectomy (n = 369, 49.2 %) was the most common primary surgery for which revision was performed. Revisional procedures performed included Roux-en-Y gastric bypass (RYGB) in 41.1 % (n = 308) patients, One anastomosis gastric bypass (OAGB) in 19.3 % (n = 145), Sleeve Gastrectomy (SG) in 16.7 % (n = 125) and other procedures in 22.9 % (n = 172) patients. Indications for revision included weight regain in 615(81.8 %) patients, inadequate weight loss in 127(16.9 %), inadequate diabetes control in 47(6.3 %) and diabetes relapse in 27(3.6 %). 30-day complications were seen in 80(10.7 %) patients. Forty-nine (6.5 %) complications were Clavien Dindo grade 3 or higher. Two patients (0.3 %) died within 30 days of RBS. Conclusion RBS for insufficient weight loss/weight regain or metabolic relapse is associated with 10.7 % morbidity and 0.3 % mortality. Sleeve gastrectomy is the most common primary procedure to undergo revisional bariatric surgery, while Roux-en-Y gastric bypass is the most commonly performed revision.

The SNP rs10487505 in the promotor region of the leptin gene was reported to be associated with decreased circulating leptin and increased body mass index (BMI). However, the phenotypic outcomes affected by rs10487505 in the leptin regulatory pathway have not been systematically studied. Therefore, the aim of this study was to elucidate the influence of rs10487505 on leptin mRNA expression and obesity-related parameters. We genotyped rs10487505 in DNA samples from 1665 patients with obesity and lean controls and measured leptin gene expression in paired samples of adipose tissue (AT, N = 310), as well as circulating leptin levels. We confirm the leptin-lowering effect of rs10487505 in women. In contrast to the previously reported data from population-based studies, in this mainly obese cohort, we describe a lower mean BMI in women carrying the C allele of rs10487505. However, no association of rs10487505 with AT leptin mRNA expression was found. Our data suggest that reduced circulating leptin levels are not a result of the direct silencing of leptin mRNA expression. Furthermore, leptin reduction by rs10487505 does not associate with BMI in a linear manner. Instead, the decreasing effect on BMI might be dependent on the severity of obesity.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the PEMT gene, including the waist–hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. PEMT expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, PEMT expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro Pemt knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in PEMT mRNA expression across the three studied tissues. Specifically, vis PEMT mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc PEMT expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT PEMT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of PEMT on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that PEMT plays a role in regulating FD and has implications in metabolic diseases.

(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) adipsin mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18–85 years; BMI: 19–70 kg/m2) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) adipsin mRNA expression by RT-PCR. (3) Results: Adipsin serum concentrations were significantly higher in patients with T2D compared to normoglycemic individuals. We found significant positive univariate relationships of adipsin serum concentrations with age (r = 0.282, p < 0.001), body weight (r = 0.264, p < 0.001), fasting plasma glucose (r = 0.136, p = 0.006) and leptin serum concentrations (r = 0.362, p < 0.001). Neither VAT nor SAT adipsin mRNA expression correlated with adipsin serum concentrations after adjusting for age, sex and BMI. Independent of T2D status, we found significantly higher adipsin expression in SAT compared to VAT (4) Conclusions: Our data suggest that adipsin serum concentrations are strongly related to obesity and age. However, neither circulating adipsin nor adipsin AT expression reflects parameters of impaired glucose or lipid metabolism in patients with obesity with or without T2D.

GRB14/COBLL1 locus has been shown to be associated with body fat distribution (FD), but neither the causal gene nor its role in metabolic diseases has been elucidated. We hypothesize that GRB14/COBLL1 may act as the causal genes for FD-related SNPs (rs10195252 and rs6738627), and that they may be regulated by SNP to effect obesity-related metabolic traits. We genotyped rs10195252 and rs6738627 in 2860 subjects with metabolic phenotypes. In a subgroup of 560 subjects, we analyzed GRB14/COBLL1 gene expression in paired visceral and subcutaneous adipose tissue (AT) samples. Mediation analyses were used to determine the causal relationship between SNPs, AT GRB14/COBLL1 mRNA expression, and obesity-related traits. In vitro gene knockdown of Grb14/Cobll1 was used to test their role in adipogenesis. Both gene expressions in AT are correlated with waist circumference. Visceral GRB14 mRNA expression is associated with FPG and HbA1c. Both SNPs are associated with triglycerides, FPG, and leptin levels. Rs10195252 is associated with HbA1c and seems to be mediated by visceral AT GRB14 mRNA expression. Our data support the role of the GRB14/COBLL1 gene expression in body FD and its locus in metabolic sequelae: in particular, lipid metabolism and glucose homeostasis, which is likely mediated by AT GRB14 transcript levels.

Background There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates. Methods We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020. Results Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country. Conclusions BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.

Background: Laparoscopic hepatectomy has gained wide acceptance in the last few years. The aim of our study is to assess the outcomes of laparoscopic liver resection between two groups matched primarily for the type and extent of hepatic resection. Methods: 268 Patients underwent liver resection in our center between 2008 and 2014, 80 laparoscopic and 188 open. A 1:1 matching was applied, based primarily on type and extent of resection and diagnosis. Perioperative and long-term outcomes were compared. Results: After matching, 65 patients were included in each group. The laparoscopic group showed lower intraoperative (p<0,001 for RBC, p=0,019 for FFP) and postoperative (p<0.001 for RBC, p=0,021 for FFP) transfusion rate, shorter hospital stay (p<0,001) and lower perioperative overall morbidity according to the Dindo-Clavien classification (p<0,001). There were no significant differences in ICU stay, negative margin rate and operative time. 30-day mortality was nil and 90-day mortality was 1,5% in both groups. For patients with colorectal metastases 2-year and 5-year disease-free survival rate was 52% and 31% for the laparoscopic group and 39% and 32% for the open group (p=0,947), whereas 2-year and 5-year overall survival rate was 81% and 46% to 70% and 39% respectively (p=0,948). Conclusion: Laparoscopic liver resection:. - is safe and feasible. - offers clear advantages compared to open hepatectomy regarding perioperative transfusion rates, hospital stay and morbidity. - has comparable long-term outcomes to open hepatecomy.

Background. Laparoscopic liver resection belongs to the standard repertoire in hepatobiliary surgery. The advantages and disadvantages are still the subject of controversial discussion. Objective. The aim of the study was to compare the perioperative and long-term outcomes of laparoscopic and open liver resections. Material and methods. All patients who underwent liver resection in the Department of Surgery at the certified liver center of the municipal hospital Karlsruhe were analyzed. From a total of 268 hepatic resections 65 laparoscopic liver resections were identified and matched 1 : 1 with 65 open resections, based primarily on the extent of the resection and secondarily on diagnosis, age and gender of the patients. The demographic data, comorbidities, perioperative and long-term outcomes were compared. Results. Both groups had comparable demographic parameters and comorbidities. Operation time, duration of intensive care stay and percentage of negative resection margins were comparable in both groups. The 30-day mortality was 0% and 90-day mortality 1.5% in both groups. The laparoscopic group showed lower intraoperative and postoperative transfusion rates (p < 0.001), shorter hospital stay (p < 0.001) and lower overall morbidity (p < 0.001). The 1-, 3- and 5-year overall and tumor-free survival of patients with colorectal liver metastases was comparable (p = 0.984; p = 0.947). The same applied for patients with hepatocellular carcinomas (p = 0.803; p = 0.935). Conclusion. Laparoscopic liver resections have identical long-term outcomes with lower overall morbidity. Laparoscopic liver resections offer advantages regarding transfusion rates, length of hospital stay and postoperative complications.

Background: Recently, sleeve gastrectomy (SG) has become one of the most important procedures in bariatric surgery. Short-term results show that SG is a feasible, safe, and effective operation treating obesity and its related co-morbidities. Now, the main focus is on long-term data after SG. Objectives: The aim of this study was to analyze perioperative and long-term results after SG in the German Bariatric Surgery Registry. Setting: National database, Germany. Methods: Perioperative data of primary SG (n=21525) and follow-up data for 5 years +/- 6 months (n=435, 18.3% of 2375 SG performed between 2005 and 2011) were analyzed. After a review of the literature long-term results were compared with international data. Results: Mean baseline body mass index (BMI) was 51.1 kg/m(2). Two hundred ninety-eight (68.5%) patients were female and 137 (31.5%) were male. Of patients, 90% had >= 1 co-morbidities. Mean operation time was 86 minutes. General postoperative complications occurred in 4.1% and special complications in 4.6% (staple-line leaks 1.6%). Mean maximum BMI loss was 18.0 +/- 6.8 kg/m(2) and BMI loss after 5 years was 14.3 +/- 7.4 kg/m(2) (P<.001). Co-morbidities, such as type 2 diabetes, hypertension, and sleep apnea, were significantly improved (P<.001). Gastroesophageal reflux was significantly impaired (P<.001). Conclusions: The current results showed that SG is a safe and effective procedure in bariatric surgery. BMI loss was significant 5 years after SG. Most co-morbidities were significantly improved, but gastroesophageal reflux has often worsened. The follow-up rate was very low, which is a persistent problem in German bariatric surgery. (C) (C) 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan (SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits. Complete DNA methylation of the SSPN promoter construct suppressed the gene expression of firefly luciferase in MCF7 cells. Moreover, rs718314 was associated with waist and with DNA methylation at CpG sites. Our data strongly support the role of the SSPN locus in body fat composition and glucose homeostasis, and suggest that this is most likely the result of changes in DNA methylation of SSPN in adipose tissue.Keller, M., Klos, M., Rohde, K., Kruger, J., Kurze, T., Dietrich, A., Schon, M. R., Gartner, D., Lohmann, T., Dre ss ler, M., Stumvoll, M., Bluher, M., Kovacs, P., Bottcher, Y. DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.

Laparoskopische Leberresektionen gehören zum Standardrepertoire der Leberchirurgie. Ihre Vor- und Nachteile werden kontrovers diskutiert.

Background/Aims: Altered expression and circulating levels of glutathione peroxidase 3 (GPX3) have been observed in obesity and type 2 diabetes (T2D) across species. Here, we investigate whether GPX3 serum concentrations and adipose tissue (AT) GPX3 mRNA expression are related to obesity and weight loss. Methods: GPX3 serum concentration was measured in 630 individuals, including a subgroup (n = 293) for which omental and subcutaneous (SC) GPX3 mRNA expression has been analyzed. GPX3 analyses include three interventions: 6 months after bariatric surgery (n = 80) or combined exercise/hypocaloric diet (n = 20) or two-step bariatric surgery (n = 24) studies. Results: Bariatric surgery-induced weight loss (–25.8 ± 8.4%), but not a moderate weight reduction of –8.8 ± 6.5% was associated with significantly reduced GPX3 serum concentrations. GPX3 mRNA is significantly higher expressed in AT from individuals with normal glucose metabolism compared to T2D patients. SC AT GPX3 expression is significantly higher in lean compared to obese as well as in insulin-sensitive compared insulin-resistant individuals with obesity. Weight loss after bariatric surgery causes a significant increase in SC AT GPX3 expression. AT GPX3 expression significantly correlates with age, BMI, fat distribution, insulin sensitivity (only SC AT), but not with circulating GPX3. Conclusion: Our data support the notion that SC AT GPX3 expression is associated with obesity, fat distribution and related to whole body insulin resistance.

Zusammenfassung Hintergrund Laparoskopische Leberresektionen gehören zum Standardrepertoire der Leberchirurgie. Ihre Vor- und Nachteile werden kontrovers diskutiert. Ziel der Arbeit Ziel dieser Studie war es, das perioperative Outcome und die langfristigen onkologischen Ergebnisse nach laparoskopischer Leberresektion mit denen konventionell offener Resektionen zu vergleichen. Material und Methoden Alle in der Klinik für Allgemein- und Viszeralchirurgie des Städtischen Klinikums Karlsruhe durchgeführten Leberresektionen wurden retrospektiv analysiert. Aus 268 Resektionen wurden 65 laparoskopische Leberresektionen identifiziert und 1:1 primär nach dem Ausmaß der Resektion und sekundär nach Diagnose, Alter und Geschlecht der Patienten mit offenen Leberresektionen gematcht. Die demographischen Daten, Komorbiditäten sowie die perioperativen und Langzeitergebnisse wurden verglichen. Ergebnisse Beide Gruppen zeigten vergleichbare Basisparameter und Komorbiditäten. Operationsdauer, Intensivaufenthalt und R0-Resektionsrate waren gleich. Die 30-Tage-Mortalität betrug in beiden Gruppen 0 %, die 90-Tage-Mortalität 1,5 %. Die laparoskopische Gruppe zeigte einen geringeren intra- sowie postoperativen Transfusionsbedarf ( p < 0,001), eine kürzere stationäre Aufenthaltsdauer ( p < 0,001) und eine geringere perioperative Gesamtmorbidität ( p < 0,001). Das 1‑, 3‑ und 5‑Jahres Gesamt- und rezidivfreie Überleben von Patienten mit kolorektalen Metastasen war in beiden Gruppen identisch ( p = 0,984; p = 0,947). Gleiche Ergebnisse zeigten sich für Patienten mit hepatozellulärem Karzinom ( p = 0,803; p = 0,935). Diskussion Mit laparoskopischen Leberresektionen können identische onkologische Ergebnisse mit niedrigerer perioperativer Morbidität erzielt werden. Laparoskopische Leberresektionen bieten deutliche Vorteile hinsichtlich des Transfusionsbedarfs, der Aufenthaltsdauer und der postoperativen Komplikationen.

Der Roux-Y-Magenbypass (LRYGB) ist ein sicheres und effektives OP-Verfahren in der Adipositaschirurgie. Dennoch werden im langfristigen postoperativen Verlauf Revisionsoperationen aufgrund von Gewichtsanstieg oder Dumping-Symptomen notwendig. Ein Grund hierfür ist u.a. eine Dilatation der Gastrojejunostomie. Diese Arbeit untersucht die Wirksamkeit der Argon-Plasma-Coagulation (APC) auf die Verkleinerung des Anastomosendurchmessers und den Einfluss auf den Gewichtsverlauf und die Dumpingsymptome.

Objective/methods: DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals.Results: We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two independent cohorts. Further, we identified six adipose tissue depot-specific genes (HAND2, HOXC6, PPARG, SORBS2, CD36, and CLDN1). The effects were further supported in additional independent cohorts. Our top hits might play a role in adipogenesis and differentiation, obesity, lipid metabolism, and adipose tissue expandability. Finally, we show that in vitro methylation of SORBS2 directly represses gene expression.Conclusions: Taken together, our data show distinct tissue specific epigenetic alterations which associate with obesity. (C) 2016 The Authors. Published by Elsevier GmbH.

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10−6), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT and SAT methylation correlated negatively with IRS1 gene expression in obese subjects (N = 16, P = 0.007 and P = 0.010). The major T-allele is related to increased DNA methylation in OVAT (N = 146, P = 0.019). Finally, DNA methylation and gene expression in OVAT correlated with anthropometric traits (waist- circumference waist-to-hip ratio) and parameters of glucose metabolism in obese individuals. Our data suggest that the association between rs2943650 near the IRS1 gene locus with clinically relevant variables may at least be modulated by changes in DNA methylation that translates into altered IRS1 gene expression.

Introduction: ALPPS-induced liver regeneration has been reported to be a catalyst of growth for preexisting, yet initially not detectable lesions in the future liver remnant (FLR). Our hypothesis is that a prolonged split-to-resection interval is a diagnostic window for detection of such lesions, thus allowing for adjustment of the therapeutic strategy. Materials and methods: Between 2011 and 2015 we applied the ALPPS Procedure on 12 patients with bilateral hepatic tumors, initially inoperable due to insufficient FLR. Results: All patients underwent a resection of metastases in the left lobe and in-situ split with ligation of the right portal vein. The mean interval between the two operations was 47 days. By the end of this interval 1 patient had developed a new metastasis in Segment 1, which was additionally resected at the second step. In 3 patients multiple new metastases were detected in the FLR. By lack of oncologic benefit no extended resection was performed; instead palliative chemotherapy was initiated immediately. 8 patients underwent an extended resection as planned. Conclusions: The prolonged split-to-resection interval allowed for a change of therapeutic strategy in 1/3 of the patients due to newly detected metastases in the FLR.

Introduction: Since the first laparoscopic liver resection in 1992, laparoscopic hepatectomy has gained wide acceptance, especially in specialized, high-volume centers. Until now, a few retrospective, matched-pair studies comparing the postoperative outcomes of laparoscopic and open liver resection have been published. However, in most cases the matched parameters were primarily age, sex, size and localization of the lesions and comorbidities. The aim of our study is to assess the perioperative outcomes of laparoscopic liver resection between two groups matched primarily for the type and extent of hepatic resection. Methods: 268 Patients underwent liver resection for benign and malignant disease in our center between 2008 and 2014, of which 80 were laparoscopically and 188 openly resected. A 1:1 matching was applied, based primarily on type and extent of resection and diagnosis. Perioperative outcomes were compared. Results: After matching, 65 patients were included in each group. There was no statistically significant difference in the baseline characteristics and comorbidities between the two groups. The laparoscopic group showed lower intraoperative (p < 0,001 for RBC, p = 0,019 for FFP) and postoperative (p < 0.001 for RBC, p = 0,021 for FFP) transfusion rate, shorter hospital stay (p < 0,001) and lower perioperative overall morbidity according to the Dindo-Clavien classification (p < 0,001). There were no significant differences in ICU stay, negative margin rate and operative time. 30-day mortality was nil and 90-day mortality was 1,5% in both groups. Conclusions: Laparoscopic liver resection is safe and feasible and offers clear advantages compared to open hepatectomy regarding perioperative transfusion rates, hospital stay and morbidity.

Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene--encoding adenylate cyclase 5--with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice. We measured ADCY5 mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 244 individuals with a wide range of body weight and parameters of hyperglycemia, which have been genotyped for rs11708067. In addition, AT ADCY5 mRNA was assessed in C57BL/6NTac which underwent a 10 weeks standard chow (n = 6) or high fat diet (HFD, n = 6). In humans, visceral ADCY5 expression is significantly higher in obese compared to lean individuals. ADCY5 expression correlates with BMI, body fat mass, circulating leptin, fat distribution, waist and hip circumference, but not with fasting plasma glucose and HbA1c. Adcy5 expression in mouse AT is significantly higher after a HFD compared to chow (p<0.05). Importantly, rs11708067 is not associated with ADCY5 mRNA expression levels in either fat depot in any of the genetic models tested. Our results suggest that changes in AT ADCY5 expression are related to obesity and fat distribution, but not with impaired glucose metabolism and T2D. However, altered ADCY5 expression in AT does not seem to be the mechanism underlying the association between rs11708067 and increased T2D risk.