The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential
Abstract
1. Introduction
2. TGR5: Structure, Expression, and Mechanism of Action
3. TGR5 Agonists
4. TGR5 in Energy Homeostasis Regulation
4.1. Hypothalamus
4.2. Brown Adipose Tissue (BAT)
4.3. White Adipose Tissue (WAT)
4.4. Skeletal Muscle
4.5. Intestine
4.6. Endocrine Pancreas
5. Clinical Approaches
6. Limitations, Challenges, and Controversies
7. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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TGR5 Agonist | EC50 (μM) | Reference |
---|---|---|
LCA | 0.53 | [32] |
DCA | 1.25 | [30] |
CDCA | 6.71 | [30] |
CA | 13.6 | [30] |
UDCA | 36.4 | [30] |
TLCA | 0.33 | [32] |
TDCA | 0.79 | [30] |
TCDCA | 1.92 | [30] |
TCA | 4.95 | [30] |
TUDCA | 30.0 | [30] |
INT-777 | 0.82 | [33] |
BAR501 | 1.0 | [34] |
SB-756050 | 1.3 | [35] |
Oleanolic acid | 2.25 | [36] |
Obacunone/Liminoid | Not specified |
TGR5 Agonist | Condition | Study Title | Clinical Trials Identifier: | Study Design, Interventions, and Location |
---|---|---|---|---|
SB756050 (GlaxoSmithKline) | Type 2 Diabetes Mellitus | A Study to Test How SB756050 Affects Subjects With Type 2 Diabetes Mellitus After 6 Days of Dosing | NCT00733577 | Study Type: Interventional Enrollment: 48 participants Phase: 1 Doses: 15 to 600 mg Duration: 6 days Placebo-Controlled Location: USA |
SB756050 (GlaxoSmithKline) | Type 2 Diabetes Mellitus | First-Time-in-Humans Study to Assess Safety, Pharmacokinetics & Pharmacodynamics of SB756050 | NCT00607906 | Study Type: Interventional Enrollment: 36 participants Phase: 1 Doses: 5–100 mg Duration: single dose Placebo-Controlled Location: USA |
Bile acid CDCA and oleanolic acid | Healthy Volunteers | Effect of Bile Acids on the Secretion of Satiation Peptides in Humans | NCT01674946 | Study Type: Interventional Enrollment: 12 participants Phase: 1 Doses: Oleanolic acid: 1–20 mM/L; CDCA: 5–15 mM/L Duration: single intraduodenal perfusion Placebo-Controlled Location: Switzerland |
Bile acid CDCA | Type 2 Diabetes Mellitus | Effect of Bile Acids on GLP-1 Secretion | NCT01666223 | Study Type: Interventional Enrollment: 20 participants Phase: Not Applicable Doses: 1250 mg Duration: single intraduodenal perfusion Placebo-Controlled Location: Denmark |
Bile acid CDCA | Metabolic Syndrome | Effects of FXR Activation on Hepatic Lipid and Glucose Metabolism | NCT00465751 | Study Type: Interventional Enrollment: 30 participants Phase: 1 Doses: 500 mg Duration: 3 months Placebo-Controlled Location: Switzerland |
Bile acid UDCA | Type 2 Diabetes Mellitus | Efficacy of Ursodeoxycholic Acid (UDCA) in Patients With Type 2 Diabetes | NCT05416580 | Study Type: Interventional Enrollment: 60 participants Phase: 3 Doses: 1500 mg Duration: 8 weeks Placebo-Controlled Location: Bosnia and Herzegovina |
Bile acid UDCA (Ursodiol) | Obesity and Type 2 Diabetes Mellitus | Ursodiol on Insulin Sensitivity, Gastric Emptying, and Body Weight With Type 2 Diabetes on Metformin | NCT02033876 | Study Type: Interventional Enrollment: 24 participants Phase: 2 Doses: 600 mg twice daily Duration: 2 weeks Placebo-Controlled Location: USA |
Bile acid TUDCA | Obesity | Effect of Endoplasmic Reticulum Stress on Metabolic Function (TUDCA/PBA) | NCT00771901 | Study Type: Interventional Enrollment: 101 participants Phase: Not Applicable Doses: 1750 mg/day Duration: 4 weeks Placebo-Controlled Location: USA |
Bile acid TUDCA | Type 2 Diabetes Mellitus | Effects of Dietary Supplement Tauroursodeoxycholic Acid on Vascular Function | NCT03331432 | Study Type: Interventional Enrollment: 8 participants Phase: Not Applicable Doses: 1750 mg/day Duration: 4 weeks Location: USA |
Oleanolic acid (olive oil) | Metabolic Diseases | Prevention With Oleanolic Acid of Insulin Resistance (PREOLIA) | NCT05049304 | Study Type: Interventional Enrollment: 22 participants Phase: Not Applicable Doses: Functional olive oil enriched in Oleanolic acid Duration: single intake Location: Spain |
Oleanolic acid (olive oil) | Type 2 Diabetes Mellitus | Oleanolic Acid as Therapeutic Adjuvant for Type 2 Diabetes Mellitus (OLTRAD STUDY) | NCT06030544 | Study Type: Interventional Enrollment: 100 participants Phase: 2 Doses: 55 mL/day of a functional olive oil enriched in Oleanolic acid Duration: 1 year Location: Spain |
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Zangerolamo, L.; Carvalho, M.; Barbosa, H.C.L. The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential. Int. J. Mol. Sci. 2025, 26, 6547. https://doi.org/10.3390/ijms26146547
Zangerolamo L, Carvalho M, Barbosa HCL. The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential. International Journal of Molecular Sciences. 2025; 26(14):6547. https://doi.org/10.3390/ijms26146547
Chicago/Turabian StyleZangerolamo, Lucas, Marina Carvalho, and Helena C. L. Barbosa. 2025. "The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential" International Journal of Molecular Sciences 26, no. 14: 6547. https://doi.org/10.3390/ijms26146547
APA StyleZangerolamo, L., Carvalho, M., & Barbosa, H. C. L. (2025). The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential. International Journal of Molecular Sciences, 26(14), 6547. https://doi.org/10.3390/ijms26146547