scholarly journals Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nadejda Bozadjieva-Kramer ◽  
Jae Hoon Shin ◽  
Yikai Shao ◽  
Ruth Gutierrez-Aguilar ◽  
Ziru Li ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Potential Role ◽  
Tissue Loss ◽  
Vertical Sleeve Gastrectomy ◽  
Lean Tissue ◽  
Gut Hormone ◽  
Improve Glucose Tolerance

AbstractBariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective improvements in obesity and Type 2 diabetes. We hypothesized a potential role for the gut hormone Fibroblast-Growth Factor 15/19 which is increased after VSG and pharmacologically can improve energy homeostasis and glucose handling. We generated intestinal-specific FGF15 knockout (FGF15INT-KO) mice which were maintained on high-fat diet. FGF15INT-KO mice lost more weight after VSG as a result of increased lean tissue loss. FGF15INT-KO mice also lost more bone density and bone marrow adipose tissue after VSG. The effect of VSG to improve glucose tolerance was also absent in FGF15INT-KO. VSG resulted in increased plasma bile acid levels but were considerably higher in VSG-FGF15INT-KO mice. These data point to an important role after VSG for intestinal FGF15 to protect the organism from deleterious effects of VSG potentially by limiting the increase in circulating bile acids.

scholarly journals Long-Term Observation of a Man With Severe Obesity and Undiagnosed Monogenic Diabetes Serendipitously Treated With Metabolic Surgery

2020 ◽  
Vol 8 ◽  
pp. 232470962097487
Author(s):  
Bhuvaneswari Pandian ◽  
Mei Chung Moh ◽  
Clara Tan ◽  
Wanxin Lai ◽  
Su Fen Ang ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Metabolic Surgery ◽  
Severe Obesity ◽  
Body Weight Loss ◽  
Diabetes Remission ◽  
Vertical Sleeve Gastrectomy ◽  
Obesity And Diabetes ◽  
The Individual ◽  
Long Term Observation

A 43-year-old man, with severe obesity (43 kg/m2) and diabetes (presumed as type 2 diabetes [T2D]), underwent vertical sleeve gastrectomy in 2009 and Roux-en-Y gastric bypass in 2013. Recently, whole exome sequencing (conducted to search for monogenic obesity) serendipitously revealed that the individual harbored a heterozygous glucokinase ( GCK) variant p.(Arg422Leu) that was bioinformatically strongly predicted to be likely pathogenic. Therefore, he is likely to have concomitant maturity-onset diabetes of the young (MODY) type 2 ( GCK-MODY). A retrospective evaluation of the clinical data showed that the subject was diagnosed with T2D (given his severe obesity) in 2005 and was treated with oral antidiabetic monotherapy. His hyperglycemia was mostly mild (HbA1c [hemoglobin] < 8.1%), consistent with that of MODY2, despite severe obesity. After vertical sleeve gastrectomy, complete diabetes remission (HbA1c <6.0% and fasting plasma glucose <5.6 mmol/L without use of antidiabetic medication) was achieved. The percentage of maximum body weight loss attained after surgery was 23.6%. Euglycemia was maintained during the subsequent decade, up to the last follow-up in 2019, without any sign of hypoglycemia. In conclusion, we report a decade-long clinical experience of a man with severe obesity and diabetes likely due to the coexistence of GCK-MODY and T2D, serendipitously treated with metabolic surgery. Interestingly, metabolic surgery was effective and safe for him.

Anorexia and fat aversion induced by vertical sleeve gastrectomy is attenuated in neurotensin receptor 1 deficient mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Cecilia Ratner ◽  
Jae-Hoon Shin ◽  
Chinmay Dwibedi ◽  
Valentina Tremaroli ◽  
Anette Bjerregaard ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Food Intake ◽  
Reduce Food Intake ◽  
Vertical Sleeve Gastrectomy ◽  
Potent Effect ◽  
Neurotensin Receptor ◽  
Macronutrient Selection ◽  
Gut Hormone ◽  
Neurotensin Receptor 1 ◽  
Fat Preference

Abstract Neurotensin (NT) is an anorexic gut hormone and neuropeptide that increases in circulation following bariatric surgery in humans and rodents. We sought to determine the contribution of NT to the metabolic efficacy of vertical sleeve gastrectomy (VSG). To explore a potential mechanistic role of NT in VSG, we performed sham or VSG surgeries in diet-induced obese neurotensin receptor 1 (NTSR1) wildtype (wt) and knockout (ko) mice and compared their weight and fat mass loss, glucose tolerance, food intake, and food preference after surgery. NTSR1 ko mice had reduced initial anorexia and body fat loss. Additionally, NTSR1 ko mice had an attenuated reduction in fat preference following VSG. Results from this study suggest that NTSR1 signaling contributes to the potent effect of VSG to initially reduce food intake following VSG surgeries and potentially also on the effects on macronutrient selection induced by VSG. However, maintenance of long-term weight loss after VSG requires signals in addition to NT.

scholarly journals THE ROLE OF THE SLEEVE GASTRECTOMY AND THE MANAGEMENT OF TYPE 2 DIABETES

2017 ◽  
Vol 30 (4) ◽  
pp. 283-286 ◽  
Author(s):  
Taíse FUCHS ◽  
Marcelo LOUREIRO ◽  
Gabriela Heloise BOTH ◽  
Heloise Helena SKRABA ◽  
Thaís Andrade COSTA-CASAGRANDE
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Glycemic Control ◽  
Published Data ◽  
Clinical Group ◽  
Vertical Sleeve Gastrectomy ◽  
Obesity And Diabetes ◽  
Pubmed Database

ABSTRACT Background : Currently, bariatric surgery has promoted weight loss and improved glycemic control in obese patients through different techniques, including vertical sleeve gastrectomy. Aim : Present and update the different vertical sleeve gastrectomy ways of action, both in the treatment of obesity and diabetes, approaching its potential effect on gastrointestinal physiology, as well as the benefits achieved by this manipulation. Methods : Pubmed database search was used crossing the headings: obesity, type 2 diabetes and sleeve gastrectomy. Results : Published data have shown that short-term weight loss tends to be higher in patients undergoing vertical sleeve gastrectomy compared to Roux-en-Y gastric bypass. In relation to glycemic control, the procedure demonstrated remission of diabetes in up to 60% after one year of surgery. After three years, however, differences in remission rate between surgical and clinical group was not observed, questioning the durability of the technical in a long-term. Conclusion : Despite showing good results, both in the weight loss and co-morbidities, conflicting results reinforce the need for more studies to prove the efficiency of the vertical sleeve gastrectomy as well as to understand its action about the molecular mechanisms involved in the disease.

scholarly journals Vertical Sleeve Gastrectomy Induces Enteroendocrine Cell Differentiation of Intestinal Stem Cells Through Farnesoid X Receptor Activation

2021 ◽  
Author(s):  
Ki-Suk Kim ◽  
Bailey C. E. Peck ◽  
Yu-Han Hung ◽  
Kieran Koch-Laskowski ◽  
Landon Wood ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Bile Acid ◽  
Bile Acids ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Vertical Sleeve Gastrectomy ◽  
Gut Peptides ◽  
Intestinal Differentiation ◽  
Intestinal Organoids

AbstractVertical sleeve gastrectomy (VSG) is one of several bariatric procedures that substantially improves glycemia and energy homeostasis. Increased secretion of multiple gut peptides has been hypothesized to be a critical contributor to VSG’s potent effects to reduce body weight and improve glucose regulation. VSG results in an increase in the number of hormone-secreting enteroendocrine cells (EECs) in the intestinal epithelium, but whether this increase is via proliferation or differentiation of EECs and their subtypes remains unclear. Notably, the beneficial effects of VSG are lost in a mouse model lacking the bile acid nuclear receptor, farnesoid X receptor (FXR). FXR is a nuclear transcription factor that has been shown to regulate intestinal stem cell (ISC) function in cancer models, but whether it plays a role specifically in normal intestinal differentiation remains unknown. Therefore, we hypothesized that the VSG-induced increase in EECs is due to changes in intestinal differentiation driven by an increase in bile acid signaling through FXR. To test this, we performed VSG in mice that express eGFP in ISC/progenitor cells and performed RNAseq on GFP-positive cells sorted from the intestinal epithelia. We also assessed changes in EEC number (marked by GLP-1) in mouse intestinal organoids following treatment with bile acids and/or an FXR antagonist. RNA-seq revealed that FXR is expressed in ISCs and that VSG explicitly alters ISC expression of several genes that regulate intestinal secretory cell development, including EEC differentiation. Mouse intestinal organoids treated with bile acids increased GLP-1-positive cell numbers, whereas a potent FXR antagonist blocked this effect. Taken together, these data indicate that VSG drives ISC fate towards EEC differentiation through FXR signaling.

scholarly journals Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice

2021 ◽  
Vol 118 (6) ◽  
pp. e2019388118
Author(s):  
Lili Ding ◽  
Eryun Zhang ◽  
Qiaoling Yang ◽  
Lihua Jin ◽  
Kyle M. Sousa ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Bile Acids ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Lipid Absorption ◽  
Metabolic Effects ◽  
Fat Absorption ◽  
Vertical Sleeve Gastrectomy ◽  
High Fat ◽  
Beneficial Effects

Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.

scholarly journals Expression of miR-206 in human islets and its role in glucokinase regulation

2018 ◽  
Vol 315 (4) ◽  
pp. E634-E637
Author(s):  
Mugdha V. Joglekar ◽  
Wilson K. M. Wong ◽  
Cody-Lee Maynard ◽  
Malati R. Umrani ◽  
David Martin ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
High Fat Diet ◽  
Potential Role ◽  
Human Islets ◽  
Β Cells ◽  
Human Diabetes ◽  
Mouse Islets ◽  
The Relationship ◽  
Important Enzyme

Inappropriate insulin secretion from β-cells is considered as an early sign of impaired glucose tolerance and type 2 diabetes (T2D). Glucokinase (GCK) is an important enzyme that regulates glucose metabolism and ensures that the normal circulating glucose concentrations are maintained. GCK expression is induced by glucose and regulated via transcription factors and regulatory proteins. Recently, microRNA-206 (miR-206) was reported to regulate GCK and alter glucose tolerance in normal and high-fat diet-fed mice. Although the study findings have implications for human diabetes, studies in human islets are lacking. Here, we analyze human islets from individuals without or with T2D, using TaqMan-based real-time qPCR at the tissue (isolated islet) level as well as at single cell resolution, to assess the relationship between miR-206 and GCK expression in normal and T2D human islets. Our data suggest that, unlike mouse islets, human islets do not exhibit any correlation between miR-206 and GCK transcripts. These data implicate the need for further studies aimed toward exploring its potential role(s) in human islets.

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