Refine
Has Fulltext
- yes (21)
Is part of the Bibliography
- yes (21)
Year of publication
Document Type
- Journal article (21) (remove)
Language
- English (21) (remove)
Keywords
- obesity (21) (remove)
Institute
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (8)
- Medizinische Klinik und Poliklinik I (6)
- Institut für Molekulare Infektionsbiologie (2)
- Institut für Psychologie (2)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (2)
- Medizinische Klinik und Poliklinik II (2)
- Pathologisches Institut (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Institut für Mathematik (1)
- Institut für Pharmakologie und Toxikologie (1)
Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI −34.3% (OP) vs. −1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.
Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m\(^2\)) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m\(^2\) (n = 110), pre-obese: 25–29.9 kg/m\(^2\) (n = 73), and obese: >30 kg/m\(^2\) (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDI\(_{vol}\) than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R\(^2\) = 0.738) and SECT (R\(^2\) = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1%) compared with non-obese (0%) and pre-obese patients (4.1%). Conclusion: DECT facilitates a 30.8% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.
Background: Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead to improvements in phase 2 clinical trials. We directly compared the effects of RYGB with a treatment using liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) in a rat model for early NAFLD. Methods: Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into the following treatment groups: RYGB, sham-operation (sham), liraglutide (0.4 mg/kg/day), PYY\(_{3-36}\) (0.1 mg/kg/day), liraglutide+PYY\(_{3-36}\), and saline. After an observation period of 4 weeks, liver samples were histologically evaluated, ELISAs and RNA sequencing + RT-qPCRs were performed. Results: RYGB and liraglutide+PYY\(_{3-36}\) induced a similar body weight loss and, compared to sham/saline, marked histological improvements with significantly less steatosis. However, only RYGB induced significant metabolic improvements (e.g., adiponectin/leptin ratio 18.8 ± 11.8 vs. 2.4 ± 1.2 in liraglutide+PYY\(_{3-36}\)- or 1.4 ± 0.9 in sham-treated rats). Furthermore, RNA sequencing revealed a high number of differentially regulated genes in RYGB treated animals only. Conclusions: The combination therapy of liraglutide+PYY\(_{3-36}\) partly mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on metabolic function lack behind RYGB.
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
Background
An intragastric balloon is used to cause weight loss in super-obese patients (BMI > 60 kg/m\(^2\)) prior to bariatric surgery. Whether weight loss from intragastric balloon influences that from bariatric surgery is poorly studied.
Methods
In this retrospective, single-center study, the effects of intragastric balloon in 26 patients (BMI 69.26 ± 6.81) on weight loss after bariatric surgery (primary endpoint), postoperative complications within 30 days, hospital readmission, operation time, and MTL30 (secondary endpoints) were evaluated. Fifty-two matched-pair patients without intragastric balloon prior to bariatric surgery were used as controls.
Results
Intragastric balloon resulted in a weight loss of 17.3 ± 14.1 kg (BMI 5.75 ± 4.66 kg/m\(^2\)) with a nadir after 5 months. Surgical and postoperative outcomes including complications were comparable between both groups. Total weight loss was similar in both groups (29.0% vs. 32.2%, p = 0.362). Direct postoperative weight loss was more pronounced in the control group compared to the gastric balloon group (29.16 ± 7.53% vs 23.78 ± 9.89% after 1 year, p < 0.05 and 32.13 ± 10.5% vs 22.21 ± 10.9% after 2 years, p < 0.05), who experienced an earlier nadir and started to regain weight during the follow-up.
Conclusion
A multi-stage therapeutic approach with gastric balloon prior to bariatric surgery in super-obese patients may be effective to facilitate safe surgery. However, with the gastric balloon, pre-treated patients experienced an attenuated postoperative weight loss with an earlier nadir and earlier body weight regain. This should be considered when choosing the appropriate therapeutic regime and managing patients’ expectations.
Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. Results: While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.
Background
Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting.
Methods
High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY\(_{3-36}\), (5) PYY\(_{3-36}\)+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed.
Results
RYGB reduced food intake and achieved sustained weight loss. Combined PYY\(_{3-36}\)+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY\(_{3-36}\)+liraglutide treatment was superior to PYY\(_{3-36}\) (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY\(_{3-36}\)+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM.
Conclusions
Liraglutide and PYY\(_{3-36}\) combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.
Chronotype is defined as the behavioral manifestation of circadian rhythms related to the external light–dark cycle. Evening chronotype has been associated with an increased risk of developing cardiometabolic diseases in obesity. Menopause is a lifestage associated with an increased risk of developing cardiometabolic diseases and a change in circadian rhythmicity compared to pre-menopause. However, the prevalence of chronotype categories in menopause and their role in determining menopause-related cardiometabolic risk, mostly in obesity, have not been investigated. Thus, we aimed to investigate the prevalence of chronotype categories in post-menopausal women with obesity and their role in menopause-related cardiometabolic risk. In this cross-sectional study we enrolled 49 pre-menopausal and 74 post-menopausal women with obesity. Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) were studied. No significance differences were detected in terms of lifestyle and adherence to the MD between pre- and post-menopausal women. Chronotype was classified as morning in 66 (53.6%), evening in 20 (16.3%) and intermediate in 37 (30.1%) women. In addition, pre-menopausal women with obesity showed a significantly higher chance to have an intermediate chronotype (OR = 2.21, 95% CI 1.28–3.83; p = 0.004), whereas post-menopausal women with obesity showed a trend to have a higher morning chronotype (OR = 1.42, 95% CI 0.98–2.06; p = 0.051), although this did not reach statistical significance. No significant differences were detected in terms of prevalence of evening chronotype between the two groups. However, the evening chronotype had a significantly higher risk to have T2DM compared to the morning (OR = 17.29, 95% CI 2.40–124.27; p = 0.005) and intermediate chronotypes (OR = 30.86, 95% CI 2.05–464.32; p = 0.013) in both pre- and post-menopausal women with obesity. In conclusion, the intermediate chronotype was significantly more prevalent in pre-menopausal women with obesity compared to post-menopausal women. Evening chronotype was associated to T2DM in both pre- and post-menopause. These results support the importance of including the assessment of chronotype in the management of women with obesity in post-menopause.
Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
(2021)
Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron‐mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high‐fat diet‐induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.
Background: Obesity is considered a risk factor for postoperative complications as it can limit exposure to the operation field, thereby significantly prolonging surgery time. Obesity-associated comorbidities, such as low-grade systemic inflammation, impaired functional status, and type 2 diabetes, are independent risk factors for impaired anastomotic wound healing and nonsurgical site infections. If obesity itself is an independent risk factor for surgical complications remains controversial, but the reason for this is largely unexplored. Summary: A MEDLINE literature search was performed using the terms: “obesity,” “excess body weight,” and “surgical complications.” Out of 65,493 articles 432 meta-analyses were screened, of which 25 meta-analyses were on the subject. The vast majority of complex oncologic procedures in the field of visceral surgery have shown higher complication rates in obese patients. Meta-analyses from the last 10 to 15 years with high numbers of patients enrolled consistently have shown longer operation times, higher blood loss, longer hospital stay for colorectal procedures, oncologic upper gastrointestinal (GI) procedures, and pancreatic surgery. Interestingly, these negative effects seem not to affect the overall survival in oncologic patients, especially in esophageal resections. A selection bias in oncologic upper GI patients may have influenced the results with higher BMI in upper GI cancer to be a predictor for better nutritional and performance status. Key Messages: Contrary to bariatric surgery, only limited evidence indicated that site and type of surgery, the approach to the abdominal cavity (laparoscopic vs. open), institutional factors, and the type of perioperative care such as ERAS protocols may play a role in determining postsurgical complications in obese patients. The initial question remains therefore partially unanswered. Large nationwide register-based studies are necessary to better understand which aspects of obesity and its related comorbidities define it as a risk factor for surgical complications.