TITLE

FXR is a molecular target for the effects of vertical sleeve gastrectomy

AUTHOR(S)
Ryan, Karen K.; Tremaroli, Valentina; Clemmensen, Christoffer; Kovatcheva-Datchary, Petia; Myronovych, Andriy; Karns, Rebekah; Wilson-Pérez, Hilary E.; Sandoval, Darleen A.; Kohli, Rohit; Bäckhed, Fredrik; Seeley, Randy J.
PUB. DATE
May 2014
SOURCE
Nature;5/8/2014, Vol. 509 Issue 7499, p183
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.
ACCESSION #
95936674

 

Related Articles

  • Diabetes improvement after bariatric surgery is dependent on weight loss. KAPLAN, LEE M.; SEELEY, RANDY J.; HARRIS, JASON L. // Bariatric Times;Apr2014, Vol. 11 Issue 4, pc14 

    The article discusses the role of bariatric surgery for the treatment of type 2 diabetes mellitus (T2DM). Topics discussed include the gastrointestinal weight loss surgical procedures for improvement of T2DM, mechanism of action of postoperative improvement in diabetes and the effects of...

  • GIP and Bariatric Surgery. Rao, Raghavendra S.; Kini, Subhash // Obesity Surgery;Feb2011, Vol. 21 Issue 2, p244 

    Bariatric surgery is the most effective modality of achieving weight loss as well as the most effective treatment for type 2 diabetes mellitus (T2DM). Glucose-dependent insulinotropic polypeptide (GIP) is an incretin and is implicated in the pathogenesis of obesity and T2DM. Its role in weight...

  • Improvement in insulin sensitivity and β-cell function following ileal interposition with sleeve gastrectomy in type 2 diabetic patients: potential mechanisms. Paula, Aureo; Stival, Alessandro; Halpern, Alfredo; DePaula, Carolina; Mari, Andrea; Muscelli, Elza; Vencio, Sergio; Ferrannini, Ele; De Paula, Aureo Ludovico; Stival, Alessandro R; DePaula, Carolina C L // Journal of Gastrointestinal Surgery;Aug2011, Vol. 15 Issue 8, p1344 

    Introduction: Bariatric surgery in morbidly obese type 2 diabetic (T2DM) patients is associated with high rates of diabetes remission. We investigated the mechanisms of the anti-diabetic effect of the laparoscopic ileal interposition with sleeve gastrectomy (LII-SG) in normal weight...

  • Role of Bile Acid Sequestrants in the Treatment of Type 2 Diabetes. HANDELSMAN, YEHUDA // Diabetes Care;May2011 Supplement 2, Vol. 34, pS244 

    The article discusses the rationale for the use of a bile acid sequestrant (BAS) to treat type 2 diabetes. It describes the clinical effects of the BAS, known as colesevelam hydrochloride, that has been approved for both glycemic and lipid control in the U.S. As new agents are approved in the...

  • A Gut Feeling to Cure Diabetes: Potential Mechanisms of Diabetes Remission after Bariatric Surgery. Young Min Cho // Diabetes & Metabolism Journal;Dec2014, Vol. 38 Issue 6, p406 

    A cure for type 2 diabetes was once a mere dream but has now become a tangible and achievable goal with the unforeseen success of bariatric surgery in the treatment of both obesity and type 2 diabetes. Popular bariatric procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy exhibit...

  • Intensified treatment with insulin detemir improved glycemic control, weight loss.  // Endocrine Today;Oct2011, Vol. 9 Issue 10, p20 

    The article reports that a randomized trial has found that adding insulin detemir to a treatment regimen of metformin and liraglutide resulted to improved glycemic control and sustained weight loss for up to 52 weeks in patients with type 2 diabetes.

  • Can 15 LB reverse diabetes? Davis, James; R.M.D. // Cortlandt Forum;11/25/95, Vol. 8 Issue 11, p87 

    Answers the question on studies proving that small weight loss can reverse adult-onset diabetes mellitus. Indication of the little effect of a small amount of weight loss.

  • The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes. Scheen, Andr� J. // Current Protein & Peptide Science;Feb2009, Vol. 10 Issue 1, p56 

    Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications. Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in...

  • Diabetes remission after bariatric surgery: is it just the incretins? Laferr&;#x00E8;re, B // International Journal of Obesity;Sep2011 Supplement, Vol. 35, pS22 

    Gastric bypass surgery (GBP) results in important and sustained weight loss and remarkable improvement of Type 2 diabetes. The favorable change in the incretin gut hormones is thought to be responsible, in part, for diabetes remission after GBP, independent of weight loss. However, the relative...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics