[Overweight and obesity in adults: general principles of treatment and conservative management]. / Übergewicht und Adipositas bei Erwachsenen: allgemeine Behandlungsgrundsätze und konservatives Management.

The prevalence of overweight and obesity is steadily increasing in Austria as well as internationally. Obesity in particular is associated with multiple health risks, comorbidities, functional disability, and social stigma. Obesity is an independent, complex, chronic disease and should be treated as such by a multidisciplinary team of appropriately qualified personnel. In addition to recent international guidelines, this consensus paper outlines the overall principles of the management of overweight and obesity and provides guidance for the diagnosis and conservative treatment, focusing on lifestyle modifications and pharmacotherapy. Using the "5A" framework of behavioral health intervention, guidelines for a structured, pragmatic, and patient-centered medical care of adults with overweight or obesity are presented.

[Indications and preoperative planning for bariatric surgery]. / Indikation und präoperative Planung zur bariatrischen Operation.

These clinical practice guidelines represent the consensus opinion of a group of Austrian specialist physicians associated with the treatment of obesity. The recommendations incorporate the current literature and guidelines and aim to balance both procedural feasibility and patient acceptance and adherence. Special emphasis was placed on simplification of the preoperative clarification and maximum patient safety. Therefore, this article makes no claim to be complete in all fields.

[Postoperative management]. / Postoperatives Management.

Bariatric surgery results in significant weight loss, reduction or even remission of obesity-associated comorbidities, reduced mortality, and improved quality of life in many patients; however, obesity is a chronic disease, thus follow-up care is required after bariatric surgery. Furthermore, specific issues, such as micronutrient deficiencies and subsequent complications, can arise both in the short-term and the long-term. Abdominal pain after bariatric surgery must always be regarded as a serious symptom. A further focus should be on the diagnosis and treatment of dumping syndrome. Patients with type 2 diabetes should be regularly screened for recurrent hyperglycemia as well as specific sequelae, even though blood glucose levels may be substantially improved or normalized. In addition to centers with multidisciplinary teams, primary care and, in particular, general practitioners will play an increasingly more important role in the follow-up care after bariatric surgery.

Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension.

BACKGROUND: In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option. METHODS: In this open-label, single-center, case-control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m2 were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs). RESULTS: We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m2 [IQR 31.4-38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (-12.0% [3.3] vs. -2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (-4 [-10.5, 0.5] vs. 0 [-3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (-16.5% [-50, 0] vs. 0% [-25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation. CONCLUSIONS: This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH.

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities. OBJECTIVES: To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity. SETTING: University hospital, Austria. METHODS: Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL). RESULTS: In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method. CONCLUSIONS: Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

The Timing of Pregnancies After Bariatric Surgery has No Impact on Children's Health-a Nationwide Population-based Registry Analysis.

PURPOSE: Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children's outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12-24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied. MATERIALS AND METHODS: A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring's data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months. RESULTS: Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval. CONCLUSION: Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children.

HbA1c and Glucose Management Indicator Discordance Associated with Obesity and Type 2 Diabetes in Intermittent Scanning Glucose Monitoring System.

Glucose management indicator (GMI) is frequently used as a substitute for HbA1c, especially when using telemedicine. Discordances between GMI and HbA1c were previously mostly reported in populations with type 1 diabetes (T1DM) using real-time CGM. Our aim was to investigate the accordance between GMI and HbA1c in patients with diabetes using intermittent scanning CGM (isCGM). In this retrospective cross-sectional study, patients with diabetes who used isCGM >70% of the time of the investigated time periods were included. GMI of four different time spans (between 14 and 30 days), covering a period of 3 months, reflected by the HbA1c, were investigated. The influence of clinical- and isCGM-derived parameters on the discordance was assessed. We included 278 patients (55% T1DM; 33% type 2 diabetes (T2DM)) with a mean HbA1c of 7.63%. The mean GMI of the four time periods was between 7.19% and 7.25%. On average, the absolute deviation between the four calculated GMIs and HbA1c ranged from 0.6% to 0.65%. The discordance was greater with increased BMI, a diagnosis of T2DM, and a greater difference between the most recent GMI and GMI assessed 8 to 10 weeks prior to HbA1c assessment. Our data shows that, especially in patients with increased BMI and T2DM, this difference is more pronounced and should therefore be considered when making therapeutic decisions.

Gestational Diabetes Mellitus in Pregnant Women with Beta-Thalassemia Minor: A Matched Case-Control Study.

Pregnancy in women with thalassemia minor is considered safe. However, a higher incidence of maternal and neonatal complications in women with the disorder has been reported in the literature. This study aimed to determine whether there is an increased risk of gestational diabetes mellitus (GDM) in pregnant women with beta-thalassemia minor. We conducted a retrospective matched case-control study of 230 pregnant women who delivered at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna between the years 2008 and 2020, whereof 115 women had beta-thalassemia minor. We found no significant difference in the occurrence of GDM between the case group and control group of age and BMI-matched healthy women. However, we observed a significantly lower hemoglobin (Hb) and hematocrit (Ht) level during the first, the second, and the third trimesters of pregnancy, and postpartum (all: p < 0.001) among women with beta-thalassemia minor compared to the healthy controls. Neonates of women with beta-thalassemia were more likely to experience post-natal jaundice and excessive weight loss (p < 0.001). We conclude that GDM is not more likely to occur in pregnant women with beta-thalassemia minor. However, clinicians should be made aware of the risk of adverse maternal and neonatal outcomes. Furthermore, women with beta-thalassemia minor should undergo regular laboratory screening and multidisciplinary pregnancy care.

Evaluation of a Bariatric Monitoring Pass for Primary Care Physicians.

INTRODUCTION: There are a growing number of patients undergoing bariatric surgery requiring lifelong follow-up. Therefore, follow-up care can no longer be covered by specialized outpatient clinics alone due to the sharp rise in the number of bariatric patients. Bariatric Patients in Primary Care: Postoperative Nutrition and Lifestyle Management (BagEL) is a survey to evaluate a newly developed structured disease management program including nutrition and lifestyle management in primary care. METHODS: The study is conceived as a randomized cohort study with a control group. An expert questionnaire for general practitioners (GPs) was developed to assess the usability of a structured postoperative care system regarding nutrition and lifestyle management for bariatric patients in primary care. A structured follow-up program in primary care with a so-called bariatric monitoring passport (BMP) was provided for patients in the intervention (INT) group and the existing information sheet "Metabolic surgery and perioperative care" for the control (CON) group. 124 patients, who met inclusion criteria and who underwent a bariatric procedure first time, served as ambassadors for delivery of the expert questionnaire and study documents to their individual GPs. RESULTS: A total of 39 (31.5%) different GPs from 124 ambassador patients responded. For the primary outcome "Does the aftercare-booklets support treatment of bariatric patients?" GPs of the INT group rated the new designed aftercare booklet (INT) significantly more helpful for treating bariatric patients than the one from the CON group (p = 0.041). DISCUSSION/CONCLUSION: These results suggest that GPs are welcoming supportive tools like our BMP to improve the care of long-term follow-up of bariatric patients and should actively participate in the development of lifelong disease management plans necessary to cope with the rapidly growing number of patients.

Trends of Overweight and Obesity in Male Adolescents: Prevalence, Socioeconomic Status, and Impact on Cardiovascular Risk in a Central European Country.

BACKGROUND: Obesity is one of the most important health-related problems of the twenty-first century. Data on its prevalence in Austria remain scarce. Aim of this study was to determine current trends of overweight and obesity, associated comorbidities and socioeconomic status in all 18-year-old male Austrian citizens, and its potential impact on the demand for bariatric surgery in the future. METHODS: Data from compulsory military conscription examinations in all 18-year-old males from 2003 to 2018 were obtained from the Federal ministry of Defense's database. Measurements of height, weight, and subsequent body mass index (BMI) calculations in 874, 220 adolescents were subdivided into yearly cohorts. Comorbidities, educational status, and nicotine abuse were evaluated. RESULTS: Mean BMI increased from 22.0 ± 3.95 kg/m2 in 2003 to 22.8 ± 4.69 kg/m2 in 2018 (p < 0.001). Overweight and obesity °I-III increased from 15.3%, 4.2%, 1.2%, and 0.4% (2003) to 20.4%, 7.1%, 2.5%, and 0.8% (2018), respectively. Cardiovascular risk, reflected by the waist-to-height ratio, increased significantly over time (p < 0.0001). Additionally, data showed a significant association of nicotine abuse in overweight or obese adolescents (p < 0.0001). Significantly less adolescents with obesity graduated from high school (p < 0.0001). Overall, 25.7% of adolescents with obesity were considered ineligible for military service. CONCLUSIONS: BMI and cardiovascular risk steadily increased over the last 15 years in Austrian male adolescents. A significant shift from normal weight to overweight was observed, while higher obesity classes doubled over this observational period. This study also revealed a significant association of BMI and lower educational status. Trends of overweight and obesity in male adolescents: prevalence, socio-economic status and impact on cardiovascular risk in a central European country.

Sex-Specific Differences in Mortality of Patients with a History of Bariatric Surgery: a Nation-Wide Population-Based Study.

PURPOSE: Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. MATERIALS AND METHODS: The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). RESULTS: In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p < 0.001(Chi-squared)). Moreover, the 30-day mortality was 0.19% and sixfold higher in men compared to women (0.48 vs. 0.08%; p < 0.001). CV (82%) and PSY (55%) were the most common comorbidities in deceased patients with no sex-specific differences. Diabetes (38%) was more common in men (43 vs. 33%; p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). CONCLUSION: After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women.

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome.

BACKGROUND/AIM: Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [18F]fluoro-2-deoxyglucose ([18F]FDG), [18F]fluoro-L-dihydroxyphenylalanine ([18F] FDOPA), and [68Ga]-DOTA-1-Nal3-octreotide ([68Ga]-DOTANOC) in ECS. PATIENTS AND METHODS: All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed. RESULTS: Collectively, 30 PET/CT examinations, 11 with [18F]FDOPA, 11 with [18F]FDG and 8 with [68Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [18F]FDG detected the tumour in 3/6 of the cases, [18F]FDOPA in 3/4, and [68Ga]GaDOTANOC in 3/3. [18F]FDOPA was the only tracer without false positive results. CONCLUSION: [68Ga]GaDOTANOC and [18F]FDOPA showed superior results compared to [18F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS.

Pre-operative Obesity-Associated Hyperandrogenemia in Women and Hypogonadism in Men Have No Impact on Weight Loss Following Bariatric Surgery.

BACKGROUND: In severe obesity, hypogonadism in men and androgen excess in women are frequently observed. Sex hormones play an important role in body composition and glucose and lipid metabolism. However, whether pre-operative gonadal dysfunction impacts weight loss after bariatric surgery is not fully known. METHODS: A total of 49 men and 104 women were included in a retrospective analysis. Anthropometric characteristics, glucose and lipid metabolism, and androgen concentrations were assessed pre-operatively and 17.9 ± 11 or 19.3 ± 12 months post-operatively in men and women. Men with (HYPOmale) and without (controls: CONmale) pre-operative hypogonadism, as well as women with (HYPERfemale) and without (controls: CONfemale) pre-operative hyperandrogenemia, were compared. RESULTS: In men, pre-operative hypogonadism was present in 55% and linked to a higher body mass index (BMI): HYPOmale 50 ± 6 kg/m2 vs. CONmale 44 ± 5 kg/m2, p = 0.001. Bariatric surgery results in comparable changes in BMI in HYPOmale and CONmale - 16 ± 6 kg/m2 vs. - 14 ± 5 kg/m2, p = 0.30. Weight loss reversed hypogonadism in 93%. In women, androgen excess was present in 22%, independent of pre-operative BMI: CONfemale 44 ± 7 kg/m2 vs. HYPERfemale 45 ± 7 kg/m2, p = 0.57. Changes in BMI were comparable in HYPERfemale and CONfemale after bariatric surgery - 15 ± 6 kg/m2 vs. - 15 ± 5 kg/m2, p = 0.88. Hyperandrogenemia was reversed in 61%. CONCLUSIONS: Besides being frequently observed, hypogonadism in men and androgen excess in women have no impact on post-surgical improvements in body weight and glucose and lipid metabolism. Weight loss resulted in reversal of hypogonadism in almost all men and of hyperandrogenemia in the majority of women.

Psychopharmacological Medication Has No Influence on Vitamin Status After Bariatric Surgery in Long-term Follow-up.

CONTEXT: A substantial number of patients undergoing bariatric surgery are prescribed psychopharmacological medication. However, the impact of concomitant psychopharmacological medication on the frequency of relevant vitamin deficiencies in postoperative follow-up is not known. METHODS: Five hundred twenty-four patients with obesity who underwent bariatric surgery (January 2004 to September 2018) with follow-up of at least 12 months, were included in retrospective analysis. Postoperative follow-up visits between January 2015 and September 2019 were analyzed. Anthropometric and laboratory data were analyzed at the first documented follow-up visit after on average 39.5 ± 37.3 months and at every following visit during the observation period. Patients with prescribed psychopharmacological drugs (PD) were compared with patients without (control group, CON). RESULTS: Psychopharmacological medication was documented in 25% (132) of patients. In 59 patients documented prescription of more than one psychiatric drug was found, whereas psychopharmacological monotherapy was found in 73 patients. Frequencies of vitamin deficiencies were comparable between PD and CON (vitamin A: p = 0.852; vitamin D: p = 0.622; vitamin E: p = 0.901; folic acid: p = 0.941). Prevalence of vitamin B12 deficiency was rare (6% CON, 1% PD) but was significantly higher in CON (p = 0.023). A comparison of CON and POLY also showed no significant differences between the groups concerning prevalence of vitamin deficiencies. CONCLUSIONS: Intake of psychopharmacological medication is highly prevalent in patients after bariatric surgery. Patients with psychopharmacological medication, who participate in structured follow-up care after bariatric surgery, are not at higher risk for vitamin deficiencies compared with controls.

Serum Myostatin is Upregulated in Obesity and Correlates with Insulin Resistance in Humans.

Obesity and type 2 diabetes mellitus have reached an epidemic level, thus novel treatment concepts need to be identified. Myostatin, a myokine known for restraining skeletal muscle growth, has been associated with the development of insulin resistance and type 2 diabetes mellitus. Yet, little is known about the regulation of myostatin in human obesity and insulin resistance. We aimed to investigate the regulation of myostatin in obesity and uncover potential associations between myostatin, metabolic markers and insulin resistance/sensitivity indices. Circulating active myostatin concentration was measured in the serum of twenty-eight severely obese non-diabetic patients compared to a sex and age matched lean and overweight control group (n=22). Insulin resistance/sensitivity was assessed in the obese group. Skeletal muscle and adipose tissue specimens from the obese group were collected during elective bariatric surgery. Adipose tissue samples from lean and overweight subjects were collected during elective abdominal surgery. Myostatin concentration was increased in obese compared to lean individuals, while myostatin adipose tissue expression did not differ. Muscle myostatin gene expression strongly correlated with expression of metabolic genes such as IRS1, PGC1α, SREBF1. Circulating myostatin concentration correlated positively with insulin resistance indices and negatively with insulin sensitivity indices. The best correlation was obtained for the oral glucose insulin sensitivity index. Our results point to an interesting correlation between myostatin and insulin resistance/sensitivity in humans, and emphasize its need for further evaluation as a pharmacological target in the prevention and treatment of obesity-associated metabolic complications.

Ultralong TE In Vivo 1 H MR Spectroscopy of Omega-3 Fatty Acids in Subcutaneous Adipose Tissue at 7 T.

BACKGROUND: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE: To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE: Prospective technical development. POPULATION: Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT: Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS: SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS: T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION: PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.

Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.

Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/ß-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis. In vitro data reveal that ABHD15 associates with and stabilizes phosphodiesterase 3B (PDE3B). Accordingly, PDE3B expression is decreased in the WAT of Abhd15-KO mice, mechanistically explaining increased protein kinase A (PKA) activity, hormone-sensitive lipase (HSL) phosphorylation, and undiminished FA release upon insulin signaling. Ultimately, Abhd15-KO mice develop insulin resistance. Notably, ABHD15 expression is decreased in humans with obesity and diabetes compared to humans with obesity and normal glucose tolerance, identifying ABHD15 as a potential therapeutic target to mitigate insulin resistance.

Adiponectin regulates aquaglyceroporin expression in hepatic stellate cells altering their functional state.

BACKGROUND AND AIM: Obesity is a major risk factor for liver fibrosis and tightly associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins are transmembrane proteins that allow the movement of water and, in case of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity; however, the mechanisms through which obesity influences HSCs activation and AQPs expression remain unclear. This study aimed to identify obesity-associated factors that are related to HSC AQPs expression activation and lipid storage. METHODS: Correlations between serum adipokine levels and hepatic AQPs gene expression were analyzed from a cohort of obese patients. AQP and fibrotic gene expression was determined in a HSC line (LX2) and in a hepatocyte cell line (HepG2) after stimulation with adiponectin using quantitative real-time polymerase chain reaction. RESULTS: We found that serum adiponectin significantly correlated with liver AQP3, AQP7, AQP9 gene expressions. In vitro, adiponectin induced upregulation of AQP3 gene and AQP3 protein expression in human HSCs, but not in hepatocytes, while AQP7, AQP9 remained undetectable. Accordingly, HSC stimulated with adiponectin increased glycerol uptake, lipogenic gene expression, and lipid storage while downregulating activation/fibrosis markers. CONCLUSIONS: These findings demonstrate that adiponectin is a potent inhibitor of HSC activation and induces AQPs expression. Thus, low serum levels of adiponectin could be a mechanism how obesity affects the functional state of HSC, thereby contributing to obesity-associated liver fibrosis.

Upregulated TNF Expression 1 Year After Bariatric Surgery Reflects a Cachexia-Like State in Subcutaneous Adipose Tissue.

BACKGROUND: Adipose tissue dysfunction contributes to obesity-associated chronic diseases. In the first year after bariatric surgery, obese patients significantly improve their metabolic status upon losing weight. We aimed to investigate whether changes in subcutaneous adipose tissue gene expression reflect a restoration of a healthy lean phenotype after bariatric surgery. METHODS: Thirty-one severely obese patients (BMI ≥ 40 kg/m2) were examined before and after surgery. subcutaneous adipose tissue (SAT) was collected during and 1 year after bariatric surgery. SAT from 20 matched lean and overweight patients (BMI < 30 kg/m2) was collected during elective abdominal surgery. Baseline characteristics and SAT gene expression relevant to glucose and lipid metabolism, inflammation, and apoptosis were analyzed. RESULTS: After surgery, mean BMI decreased from 46.1 ± 6.3 to 31.1 ± 5.7 kg/m2 and homeostasis model assessment of insulin resistance from 5.4 ± 5.3 to 0.8 ± 0.8. SAT expression of most analyzed inflammatory cytokines, growth factors, and metabolic and cell surface markers was greatly downregulated even compared to the lean cohort. In contrast, gene expression of TNF and CASP3 was significantly upregulated. Elastic net regression analysis showed that fasting glucose levels and CASP3 predicted increased TNF expression in the post-obese group. CONCLUSIONS: Gene expression patterns in SAT 1 year after bariatric surgery point to a reduced inflammation. The unexpected high TNF expression in SAT of post-obese subjects is most likely not an indicator for inflammation, but rather an indicator for increased lipolysis and adipose tissue catabolism. Notably, after bariatric surgery SAT gene expression reflects a cachexia-like phenotype and differs from the lean state.