scholarly journals Are peptide conjugates the golden therapy against obesity?

2018 ◽  
Vol 238 (2) ◽  
pp. R109-R119 ◽  
Author(s):  
S J Brandt ◽  
M Kleinert ◽  
M H Tschöp ◽  
T D Müller

Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.

2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.


2021 ◽  
Author(s):  
Arnaud Liagre ◽  
Francesco Martini ◽  
Radwan Kassir ◽  
Gildas Juglard ◽  
Celine Hamid ◽  
...  

Abstract Purpose The treatment of people with severe obesity and BMI > 50 kg/m2 is challenging. The present study aims to evaluate the short and mid-term outcomes of one anastomosis gastric bypass (OAGB) with a biliopancreatic limb of 150 cm as a primary bariatric procedure to treat those people in a referral center for bariatric surgery. Material and Methods Data of patients who underwent OAGB for severe obesity with BMI > 50 kg/m2 between 2010 and 2017 were collected prospectively and analyzed retrospectively. Follow-up comprised clinical and biochemical assessment at 1, 3, 6, 12, 18, and 24 months postoperatively, and once a year thereafter. Results Overall, 245 patients underwent OAGB. Postoperative mortality was null, and early morbidity was observed in 14 (5.7%) patients. At 24 months, the percentage total weight loss (%TWL) was 43.2 ± 9, and percentage excess weight loss (%EWL) was 80 ± 15.7 (184 patients). At 60 months, %TWL was 41.9 ± 10.2, and %EWL was 78.1 ± 18.3 (79 patients). Conversion to Roux-en-Y gastric bypass was needed in three (1.2%) patients for reflux resistant to medical treatment. Six patients (2.4%) had reoperation for an internal hernia during follow-up. Anastomotic ulcers occurred in three (1.2%) patients. Only two patients (0.8%) underwent a second bariatric surgery for insufficient weight loss. Conclusion OAGB with a biliopancreatic limb of 150 cm is feasible and associated with sustained weight loss in the treatment of severe obesity with BMI > 50 kg/m2. Further randomized studies are needed to compare OAGB with other bariatric procedures in this setting. Graphical abstract


Author(s):  
Manish Khaitan ◽  
Riddhish Gadani ◽  
Koshish Nandan Pokharel

<b><i>Objectives:</i></b> The growing prevalence of obesity rates worldwide is associated with an upsurge in its comorbidities, particularly type 2 diabetes mellitus (T2DM). Bariatric surgery is a proven treatment modality for producing sustained weight loss and resolution of associated T2DM providing marked improvement in quality of life with rapid recovery. This study aims to investigate the effects of laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and mini-gastric bypass (MGB) on obese patients suffering from T2DM in the Indian population and their long-term association with regard to diabetes remission, resolution of comorbidities, and percentage EWL. <b><i>Methods:</i></b> Retrospective data of obese patients with T2DM (preoperative BMI 45.37 ± 8.1) who underwent bariatric surgery (RYGB, LSG, and MGB) were analyzed in this study over a period of 9 years. The mean follow-up period was 2.2 years. Following surgery, the clinical outcome on BMI, resolution of percentage weight loss, and T2DM were studied. The predictive factors of diabetic remission after surgery were determined. Student’s <i>t</i> test and ANOVA and McNemar’s test were applied. <b><i>Results:</i></b> Out of a total of 274 patients, complete remission of T2DM was achieved in 52.9% (<i>n</i> = 145) with mean fasting blood glucose and glycated hemoglobin values being 6.1 ± 0.769 (<i>p</i> = 0.00) at 1 year after surgery. The independent predictive factors of remission were age, gender, BMI, preoperative comorbidities, and % EWL. Gender had no correlation with the chance of achieving disease remission. <b><i>Conclusion:</i></b> Based on our results, bariatric surgery proves to be a successful treatment option resulting in sustained weight loss in obese patients suffering from T2DM. It is found to be beneficial for the long-term resolution of T2DM and improving comorbidities such as hypertension and dyslipidemia. The outcome of the different surgical methods is found to be similar for all patients irrespective of the independent predictors of complete remission.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Afshan Masood ◽  
Lujain Alsheddi ◽  
Loura Alfayadh ◽  
Bushra Bukhari ◽  
Ruba Elawad ◽  
...  

Bariatric surgery is considered to be an effective treatment for the resolution of severe obesity; however, in more than half of the bariatric surgery patients, weight reacquisition occurs as early as 18 months postsurgery, compromising the surgery’s beneficial effects. Maintaining weight loss after surgery poses a great challenge, necessitating the identification of predicting factors. In the present study, we explored the association between weight regain and dietary habits and behavioral lifestyle practices in patients following bariatric surgery. Fifty patients who underwent bariatric surgery with ≥18-month postoperative period of follow-up were included. They were classified into two groups: weight maintainers (n = 29) were patients who regained <15% of their weight, and weight regainers (n = 21) were patients who regained ≥15% of their weight compared to their lowest postoperative weight. The mean age of the study participants was 41.4 ± 8.9 years, and twenty-eight patients (56%) of the total, were females. A detailed analysis of dietary and lifestyle habits was performed by questionnaire-based interviews. Significant weight regain was noted in the regainers compared to the maintainers (19.6 ± 8.4 kg vs. 4.5 ± 3.5 kg, respectively, P≤0.001), which was attributed to their following of unhealthy dietary habits and behavioral lifestyle practices. The dietary and behavioral lifestyle practices adopted by the maintainers were higher fiber consumption and water intake, monitored pace of eating, evasion of emotional binge, and distracted eating and following of self-assessment behaviors. Additionally, regular nutritional follow-ups and compliance with postoperative dietary counseling significantly helped to improve weight maintenance. In conclusion, the effectiveness of weight loss postbariatric surgery was compromised by weight regain due to unhealthy dietary and behavioral lifestyle practices stemming from a lack of nutritional guidance and knowledge. The implementation of comprehensive nutritional counseling and advice on behavioral changes before and after surgery will help achieve optimal weight results.


2013 ◽  
Vol 6 (2) ◽  
pp. 124-130
Author(s):  
Dorothy Roedel Ferraro

Adolescent obesity and obesity-related conditions have risen at alarming rates in the United States, positioning childhood obesity as a major public health issue. The consequences of adolescent obesity are far-reaching and often include medical, psychosocial, emotional, and economic burdens. Traditional interventions targeted at diet and behavior modification are largely ineffective in reducing adolescent adiposity. Bariatric surgery, therefore, is gaining recognition as a means to significant and sustained weight loss in the teenage population. Given the innovative nature of this intervention and the lack of robust evidence to support its safety and efficacy in this population, few procedures are being performed on pediatric patients. Surgical weight loss in young patients with severe obesity poses a staid ethical burden to all involved. This article addresses the ethical issues of beneficence and nonmaleficence as they apply to adolescent bariatric surgery. Bariatric surgery for the treatment of severe adolescent obesity is an ethical and effective approach when performed discriminately in centers that can provide expert interprofessional support.


Author(s):  
Andrea Deledda ◽  
Stefano Pintus ◽  
Andrea Loviselli ◽  
Michele Fosci ◽  
Giovanni Fantola ◽  
...  

The obesity epidemic, mainly due to lifestyle changes in recent decades, leads to serious comorbidities that reduce life expectancy. This situation is affecting the health policies of many nations around the world. Traditional measures such as diet, physical activity, and drugs are often not enough to achieve weight loss goals and to maintain the results over time. Bariatric surgery (BS) includes various techniques, which favor rapid and sustained weight loss. BS is a useful and, in most cases, the best treatment in severe and complicated obesity. In addition, it has a greater benefit/risk ratio than non-surgical traditional therapies. BS can allow the obese patient to lose weight quickly compared with traditional lifestyle changes, and with a greater probability of maintaining the results. Moreover, BS promotes improvements in metabolic parameters, even diabetes remission, and in the quality of life. These changes can lead to an increase of life expectancy by over 6 years on average. The nutrition of people before and after BS must be the subject of indications from a trained staff, and patients must be followed in the subsequent years to reduce the risk of malnutrition and the associated problems. In particular, it is still debated whether it is necessary to lose weight prior to surgery, a procedure that can facilitate the surgeon’s work reducing the surgical risk, but at the same time, lengthens preparation times increasing the risks associated with concomitant pathologies. Furthermore, preventing nutritional deficiencies prior to the intervention can improve the results and reduce short- and long-term mortality.


2015 ◽  
Vol 241 (1) ◽  
pp. e220
Author(s):  
C. Ebenbichler ◽  
A. Melmer ◽  
W. Sturm ◽  
C. Ress ◽  
A. Tschoner ◽  
...  

2020 ◽  
Author(s):  
Ana BF Emiliano ◽  
Ying He ◽  
Sei Higuchi ◽  
Rabih Nemr ◽  
Natalie Lopatinsky ◽  
...  

AbstractBackgroundSleeve gastrectomy (SG) is currently the most frequently performed bariatric surgery in the United States. The majority of patients undergoing SG are middle aged women. Most preclinical models of bariatric surgery, however, utilize juvenile male mice. A long-term characterization of the response of mature wild type, obese female mice to SG has not been performed. Thus, we set out to characterize the response of middle aged obese female mice to SG.MethodsTen-month old C57bl/6J obese female mice were randomized to undergo SG, sham surgery without caloric restriction (SH) or sham surgery with caloric restriction to match body weight to the SG group (SWM). Body weight, body composition and glucose tolerance were matched at baseline. Mice were followed for 60 days following their respective surgeries.ResultsThe SG group had a more pronounced percent weight loss than the SH and SWM control groups (p<0.05), while consuming more calories than the SWM group (p<0.05). The SG group had a significant improvement in glucose tolerance compared to the SH control group (p<0.05). Plasma leptin was significantly decreased in the SG and SWM group, compared to the SH group (p<0.01). Unexpectedly, FGF-21 was increased in the SH group compared to the SG and SWM groups (p<0.01), while there was no difference in plasma insulin among the three groups. Heat production was increased in the SG group compared to SWM and SH groups (p<0.001). SG also had a significantly increased mRNA expression of Uncoupling Protein 1 (UCP-1), Adiponectin and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC1-alpha) in brown adipose tissue (BAT), compared to SWM and SH groups. Both SG and SWM groups had increased fecal lipid excretion (p<0.05), compared to the SH group.ConclusionsSG in obese, middle aged female mice leads to sustained weight loss and blood glucose improvement. It appears that increased metabolism in BAT may be linked to these effects.


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