Restored TDCA and valine levels imitate the effects of bariatric surgery

Background: Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities. Methods: Metabolic profiling was performed on diet induced obese (DIO) mice, lean mice and DIO mice that underwent sleeve gastrectomies. In addition, mice were subjected to i.p. injections with TDCA and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with an MCH antagonist and intrathecal administration of melanin-concentrating hormone were performed and weight loss was monitored. Results: Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-Valine levels were restored after sleeve gastrectomies (SGx) in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the melanin-concentrating hormone. Conclusions: In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.

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Restored TDCA and Valine Levels Imitate the Effects of Bariatric Surgery

10.1101/2021.01.11.425291 ◽

2021 ◽

Author(s):

Markus Quante ◽

Jasper Iske ◽

Timm Heinbokel ◽

Bhavna N. Desai ◽

Hector Rodriguez Cetina Biefer ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Metabolic Disorders ◽

Underlying Mechanism ◽

Diet Induced Obesity ◽

Metabolomic Profiling ◽

Sustained Weight Loss ◽

Central Inhibition ◽

Melanin Concentrating Hormone

AbstractObesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities.We performed sleeve-gastrectomies (SGx) in a pre-clinical mouse model of diet-induced obesity (DIO), delineating the effects on long-term remission from obesity. SGx resulted in sustained weight loss and improved glucose tolerance. Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of taurodeoxycholic acid (TDCA) and L-valine in DIO mice. Notably, TDCA and L-Valine levels were restored after SGx in both human and mice to levels comparable with lean controls.Strikingly, combined systemic treatment with TDCA and valine induced a profound weight loss in DIO mice analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the melanin-concentrating hormone.In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.

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Is One Anastomosis Gastric Bypass with a Biliopancreatic Limb of 150 cm Effective in the Treatment of People with Severe Obesity with BMI > 50?

Obesity Surgery ◽

10.1007/s11695-021-05499-3 ◽

2021 ◽

Author(s):

Arnaud Liagre ◽

Francesco Martini ◽

Radwan Kassir ◽

Gildas Juglard ◽

Celine Hamid ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Gastric Bypass ◽

Severe Obesity ◽

Postoperative Mortality ◽

One Anastomosis Gastric Bypass ◽

Sustained Weight Loss ◽

Biliopancreatic Limb ◽

Percentage Excess Weight Loss

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

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Evaluation of the Effects of Bariatric Surgery in Terms of Weight Loss and Diabetes Remission in the Indian Population

Dubai Diabetes and Endocrinology Journal ◽

10.1159/000518856 ◽

2021 ◽

pp. 1-7

Author(s):

Manish Khaitan ◽

Riddhish Gadani ◽

Koshish Nandan Pokharel

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Gastric Bypass ◽

Complete Remission ◽

Predictive Factors ◽

Indian Population ◽

Diabetes Remission ◽

Obese Patients ◽

Sustained Weight Loss

Objectives: 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. Methods: 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 t test and ANOVA and McNemar’s test were applied. Results: Out of a total of 274 patients, complete remission of T2DM was achieved in 52.9% (n = 145) with mean fasting blood glucose and glycated hemoglobin values being 6.1 ± 0.769 (p = 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. Conclusion: 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.

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Are peptide conjugates the golden therapy against obesity?

Journal of Endocrinology ◽

10.1530/joe-18-0264 ◽

2018 ◽

Vol 238 (2) ◽

pp. R109-R119 ◽

Cited By ~ 10

Author(s):

S J Brandt ◽

M Kleinert ◽

M H Tschöp ◽

T D Müller

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Small Subset ◽

New Era ◽

Beneficial Effects ◽

New Class ◽

Sustained Weight Loss ◽

Obesity Therapy ◽

Glucagon Like Peptide 1 ◽

The Way

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.

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The Ethical Dilemma of Adolescent Bariatric Surgery

Clinical Scholars Review ◽

10.1891/1939-2095.6.2.124 ◽

2013 ◽

Vol 6 (2) ◽

pp. 124-130

Author(s):

Dorothy Roedel Ferraro

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Ethical Issues ◽

Young Patients ◽

The United States ◽

Adolescent Obesity ◽

Public Health Issue ◽

Sustained Weight Loss ◽

And Behavior ◽

Adolescent Bariatric Surgery

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.

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Nutritional Management in Bariatric Surgery Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182212049 ◽

2021 ◽

Vol 18 (22) ◽

pp. 12049

Author(s):

Andrea Deledda ◽

Stefano Pintus ◽

Andrea Loviselli ◽

Michele Fosci ◽

Giovanni Fantola ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Life Expectancy ◽

Diabetes Remission ◽

Lifestyle Changes ◽

Nutritional Deficiencies ◽

Obesity Epidemic ◽

Sustained Weight Loss ◽

Before And After ◽

Reduce Life Expectancy

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.

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Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

10.20944/preprints202102.0243.v1 ◽

2021 ◽

Author(s):

Mohammed K. Hankir ◽

Laura Rotzinger ◽

Arno Nordbeck ◽

Caroline Corteville ◽

Annett Hoffmann ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Body Weight ◽

Food Intake ◽

Glucose Tolerance ◽

Leptin Receptor ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Sustained Weight Loss ◽

Obese Rats

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of endogenous leptin action. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

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Effects of pronounced and sustained weight loss induced by bariatric surgery on PCSK-9 plasma concentrations

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.1032 ◽

2015 ◽

Vol 241 (1) ◽

pp. e220

Author(s):

C. Ebenbichler ◽

A. Melmer ◽

W. Sturm ◽

C. Ress ◽

A. Tschoner ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Plasma Concentrations ◽

Sustained Weight Loss

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Sleeve gastrectomy promotes sustained weight loss while increasing heat production in middle aged, obese female mice

10.1101/2020.10.04.325787 ◽

2020 ◽

Author(s):

Ana BF Emiliano ◽

Ying He ◽

Sei Higuchi ◽

Rabih Nemr ◽

Natalie Lopatinsky ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Body Weight ◽

Sleeve Gastrectomy ◽

Middle Aged ◽

Female Mice ◽

Sham Surgery ◽

Obese Female ◽

Sustained Weight Loss ◽

Sh Group

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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The Gut Hormones in Appetite Regulation

Journal of Obesity ◽

10.1155/2011/528401 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 44

Author(s):

Keisuke Suzuki ◽

Channa N. Jayasena ◽

Stephen R. Bloom

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Food Intake ◽

Peptide Yy ◽

Critical Role ◽

Gut Hormones ◽

Energy Status ◽

Increased Risk ◽

Glucagon Like Peptide 1

Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight.

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