Tas2r138-KO Mouse

Tas2r138, a member of the G-protein-coupled bitter receptor family, is not only involved in sensing taste but also has diverse functions [1]. It is widely distributed in organs like the respiratory tract, gut, and lungs, in addition to the tongue and nasal cavity. Bitter receptors can detect pathogenic organisms due to their sensitivity to foreign substances, and Tas2r138 may play a role in this regard [1].

In the context of Pseudomonas aeruginosa infection, through in vivo studies likely involving gene-related research models (implied by the functional discovery), Tas2r138 was found to facilitate lipid droplet degradation in neutrophils. It does this by competitively binding with PPARG antagonist: N-(3-oxododecanoyl)-L-homoserine lactone (AHL-12), a virulence-bound signal of P. aeruginosa. This releases PPARG to migrate to the cytoplasm and accelerate lipid droplet degradation by binding PLIN2. The TAS2R138-AHL-12 complex then targets lipid droplets for enhanced degradation, helping clear AHL-12 in neutrophils and maintain local homeostasis [1]. In intestinal STC-1 cells, hop bitter compounds can increase the expression of Tas2r138, and this may be related to the regulation of orexigenic and anorexigenic peptide secretion, potentially being a target for controlling food intake and obesity prevalence [2]. Also, in a high-fat diet (HFD)-induced obesity mouse model, the mRNA of Tas2r138 was significantly increased after 8 weeks of HFD feeding, an effect prevented by antibiotics, indicating a microbiota-dependent upregulation [3]. In addition, a hydroalcoholic hop extract can interact with Tas2r138 in STC-1 cells, mediating the secretion of anorexigenic peptides in a calcium-dependent manner, with potential applications in preventing or combating obesity [4].

In conclusion, Tas2r138 has essential functions in host immunity against P. aeruginosa infection by facilitating lipid droplet degradation in neutrophils. It also plays a role in the regulation of appetite-related peptide secretion, potentially influencing obesity-related conditions. Studies using mouse models, such as those related to HFD-induced obesity, have revealed its microbiota-dependent regulation. These findings help in understanding the biological functions of Tas2r138 and its potential implications in infectious diseases and obesity-related research.

References:

1. Pu, Qinqin, Guo, Kai, Lin, Ping, Xia, Zhenwei, Wu, Min. 2021. Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection. In Signal transduction and targeted therapy, 6, 210. doi:10.1038/s41392-021-00602-7. https://pubmed.ncbi.nlm.nih.gov/34083514/

2. Lela, Ludovica, Ponticelli, Maria, Carlucci, Vittorio, Tzvetkov, Nikolay T, Milella, Luigi. 2024. Insight into the Interaction of Humulus lupulus L. Specialized Metabolites and Gastrointestinal Bitter Taste Receptors: In Vitro Study in STC-1 Cells and Molecular Docking. In Journal of natural products, 87, 2021-2033. doi:10.1021/acs.jnatprod.4c00532. https://pubmed.ncbi.nlm.nih.gov/39126694/

3. Caremoli, Filippo, Huynh, Jennifer, Lagishetty, Venu, Jacobs, Jonathan P, Sternini, Catia. 2023. Microbiota-Dependent Upregulation of Bitter Taste Receptor Subtypes in the Mouse Large Intestine in High-Fat Diet-Induced Obesity. In Nutrients, 15, . doi:10.3390/nu15194145. https://pubmed.ncbi.nlm.nih.gov/37836428/

4. Lela, Ludovica, Carlucci, Vittorio, Kioussi, Chrissa, Milella, Luigi, Russo, Daniela. 2024. Humulus lupulus L.: Evaluation of Phytochemical Profile and Activation of Bitter Taste Receptors to Regulate Appetite and Satiety in Intestinal Secretin Tumor Cell Line (STC-1 Cells). In Molecular nutrition & food research, 68, e2400559. doi:10.1002/mnfr.202400559. https://pubmed.ncbi.nlm.nih.gov/39388530/