Muscle regulatory factors regulate T1R3 taste receptor expression

Kokabu, Shoichiro; Lowery, Jonathan W.; Toyono, Takashi; Seta, Yuji; Hitomi, Suzuro; Sato, Tsuyoshi; Enoki, Yuichiro; Okubo, Masahiko; Fukushima, Yukio; Yoda, Tetsuya

doi:10.1016/j.bbrc.2015.10.142

Cited by 25 publications

(28 citation statements)

References 38 publications

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“…Simon et al [16] and addresses the open question regarding the cellular mechanism(s) underlying high bone mass in mice. Although Tas1R3 expression has been previously observed in the skeleton [10], we are the first to detail the specific skeletal cell types that express TAS1R family members in vitro. In particular, Tas1R3 and Tas1R2 are expressed endogenously in murine osteoclast precursors, and their expression levels parallel the robust increase in the osteoclast marker Ctsk during osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 98%

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

et al. 2017

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The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling.

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Section: Discussionmentioning

confidence: 98%

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

et al. 2017

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“…T1R2−/− knockout mice had decreased numbers of adipocytes in the bone marrow microenvironment [218]. Muscle regulatory factors (e.g., myogenin) might control myogenesis and skeletal muscle metabolism through the regulation of T1R3 expression [219]. T1R3−/− knockout mice showed reduced degree of mTORC1 activation and increased rate of autophagy in the skeletal muscle, suggesting the role of T1R3 in tissue nutrition and normal development [220].…”

Section: Traditional Taste (Rasa) In the Light Of Modern Sciencementioning

confidence: 99%

Extraoral Taste Receptor Discovery: New Light on Ayurvedic Pharmacology

Gîlcă

Dragoș

2017

Evidence-Based Complementary and Alternative Medicine

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More and more research studies are revealing unexpectedly important roles of taste for health and pathogenesis of various diseases. Only recently it has been shown that taste receptors have many extraoral locations (e.g., stomach, intestines, liver, pancreas, respiratory system, heart, brain, kidney, urinary bladder, pancreas, adipose tissue, testis, and ovary), being part of a large diffuse chemosensory system. The functional implications of these taste receptors widely dispersed in various organs or tissues shed a new light on several concepts used in ayurvedic pharmacology (dravyaguna vijnana), such as taste (rasa), postdigestive effect (vipaka), qualities (guna), and energetic nature (virya). This review summarizes the significance of extraoral taste receptors and transient receptor potential (TRP) channels for ayurvedic pharmacology, as well as the biological activities of various types of phytochemical tastants from an ayurvedic perspective. The relative importance of taste (rasa), postdigestive effect (vipaka), and energetic nature (virya) as ethnopharmacological descriptors within Ayurveda boundaries will also be discussed.

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“…Although this amino acid receptor is believed to affect insulin production and glycemic control, it has classically been thought to have a more potent intestinotrophic and mucosal protective effects through release of intestinal hormones and by increasing the rate of duodenal bicarbonate secretion, at least partially mediated by GLP-2, which is released from umami receptor expressing L-cells [25]. These findings implicate nutrient chemosensing as a means to enhance mucosal defenses.…”

Section: Taste Receptor-related Release Of Glpsmentioning

confidence: 99%

“…Although umami receptor components have evolutionarily conserved sequences, their expression varies widely dependent on the presence of distinct metabolic processes. For example, skeletal muscle components MyoD and myogenin modulate TAS1R3 promoter activity with consequent muscle growth and metabolism, which in turn affects intestinal umami receptor expression and nutrient chemosensing in the intestines [25]. This variation in receptor expression may affect intestinal physiology, such as the peristaltic movement of the colonic content and the peristaltic reflex – both of which are accelerated via umami receptor activation [26].…”

Section: Taste Receptor-related Release Of Glpsmentioning

confidence: 99%

Gastrointestinal defense mechanisms

Said

Kaunitz

2016

Current Opinion in Gastroenterology

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Purpose of Review To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). Recent Findings There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon-derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLPs 1 & 2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreaticβcells, but also has been implicated in having trophic effects on the intestinal epithelium. Additionally, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion in order to improve gastric mucosal health and longevity. Summary Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 & -2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury.

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Muscle regulatory factors regulate T1R3 taste receptor expression

Cited by 25 publications

References 38 publications

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

Extraoral Taste Receptor Discovery: New Light on Ayurvedic Pharmacology

Gastrointestinal defense mechanisms

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