The TGR5 Receptor and metabolic disease

Tue, 05/17/2016 - 12:43

The bile acid-responsive G-protein-coupled receptor TGR5 is widely distributed across the human body - including the endocrine glands, adipocyte cells, muscles, immune organs, spinal cord, and the enteric nervous system. G protein coupled receptors (GPCRs) are incredibly versatile signaling molecules that are activated by a number of ligands, which in turn regulate various signaling pathways. Select G proteins stimulate activity, whereas others have inhibitory effects.  The effect of TGR5 activation depends on the tissue where it is expressed and the signaling cascade that it induces.  Specifically, bile acids initiate the activation of the TGR5 receptor.  BA’s primary role are to facilitate the uptake and absorption of lipids, making their receptors important for bile acid synthesis and metabolism, as well as integration of multiple homeostatic functions in the liver and gastrointestinal tract.  Since its discovery, TGR5 has been specifically implicated in basal metabolism and energy expenditure, making it a potential therapeutic target for the treatment of metabolic disorders, such as heart disease and diabetes. 

TGR5 antibody

Immunohistochemistry-Paraffin: TGR5 Antibody [NBP1-39749] - Staining of human colon. Immunohistochemistry of formalin-fixed, paraffin-embedded tissue after heat-induced antigen retrieval. Antibody concentration 10 ug/ml.

Cipriani et al took a closer look at how the TGR5 receptor may or may not modulate the integrity of the intestine after introduction of colitis.  Their group first found that by using a TGR5 antibody that TGR5 was diffusely expressed in intact colon, and its absence led to structural changes in the colon structure and function.  They also used a TGR5 antibody (NBP1-39749) to show that TGR5 levels changed in response to inflammation.  These findings correspond to research that TGR5 mRNA is found in both leukocytes and monocytes.  Cipriani’s group also used a TGR5 antibody (NBP1-39749) to check whether there was a correlation between increased mucosal protection in the intestine in response to inflammation caused by the overuse of NSAID’s.  Ultimately they concluded that TGR5 was in fact required for intestinal mucosal integrity, and is thought to act via a COX dependent pathway.  Other research groups have used a TGR5 antibody to show expression of TGR5 in brown adipocyte tissues (BATs), which may introduce novel therapies to target the TGR5 receptor to specifically regulate thermogenesis.  Currently, activation of TGR5 through bile acids increases energy expenditure and thus slows insulin resistance and onset obesity. 

As expected, GPCRs are a highly dynamic family of proteins that have the power to modulate a vast range of signaling pathway depending on the location of protein expression and available ligand.  At the same time, bile acids are also interesting molecules that have implications in not only GPCR pathways, but both kinase and nuclear receptor related pathways as well.  Together, the TGR5 receptor and bile acid pathway has potential to be involved in heart disease, diabetes, obesity, intestinal inflammation, and more. 

Novus Biologicals offers TGR5 reagents for your research needs including:


  1. PMID: 24411485
  2. PMID: 22162464
  3. PMID: 22881598

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