Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion

2014 ◽  
Vol 70 (3) ◽  
pp. 667-674 ◽  
Author(s):  
Pablo Quintero ◽  
Margarita Pizarro ◽  
Nancy Solís ◽  
Juan Pablo Arab ◽  
Oslando Padilla ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Acid Supplementation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Oleoylethanolamide modulates glucagon-like peptide-1 receptor agonist signaling and enhances exendin-4-mediated weight loss in obese mice

2018 ◽  
Vol 315 (4) ◽  
pp. R595-R608 ◽  
Author(s):  
Jacob D. Brown ◽  
Danielle McAnally ◽  
Jennifer E. Ayala ◽  
Melissa A. Burmeister ◽  
Camilo Morfa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Expenditure ◽  
Receptor Agonist ◽  
Day Treatment ◽  
Mtor Pathway ◽  
Obese Mice ◽  
Promote Weight Loss ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA), such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt, mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote phosphorylation of mTOR pathway components, but OEA does not enhance this effect. OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO) mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to transient hypophagia and increased energy expenditure, phenotypes also observed in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling but appears to work in parallel with Ex4 to promote weight loss in DIO mice. Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could, therefore, be leveraged toward more effective obesity therapies.

scholarly journals Single-Dose Metformin Enhances Bile Acid–Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes

2017 ◽  
Vol 102 (11) ◽  
pp. 4153-4162 ◽  
Author(s):  
Andreas Brønden ◽  
Anders Albér ◽  
Ulrich Rohde ◽  
Jens F Rehfeld ◽  
Jens J Holst ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Dose ◽  
Bile Acid ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Remission of Bile Acid Malabsorption Symptoms Following Treatment With the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide

2019 ◽  
Vol 157 (2) ◽  
pp. 569-571
Author(s):  
Martin L. Kårhus ◽  
Andreas Brønden ◽  
Michael E. Røder ◽  
Salvatore Leotta ◽  
David P. Sonne ◽  
...  
Keyword(s):  
Bile Acid ◽  
Receptor Agonist ◽  
Bile Acid Malabsorption ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Reversal of Obesity and Insulin Resistance by a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist in Diet-Induced Obese Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e14205 ◽  
Author(s):  
Min He ◽  
Haoran Su ◽  
Weiwei Gao ◽  
Stina M. Johansson ◽  
Qing Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Receptor Agonist ◽  
Obese Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?

2010 ◽  
Vol 299 (1) ◽  
pp. E10-E13 ◽  
Author(s):  
Filip K. Knop
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Secretion ◽  
Postprandial Glucose ◽  
Glucose Lowering ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.

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