GPR41 and GPR43: From development to metabolic regulation

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116735 - 116735

Published: May 13, 2024

G-protein-coupled receptors are a diverse class of cell surface that orchestrate numerous physiological functions. The receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which metabolites dietary fermentation by the host's intestinal bacteria. These have gained attention as potential therapeutic targets against various diseases because their SCFA-mediated beneficial effects on health. Mounting evidence has associated activity these with chronic metabolic diseases, including obesity, diabetes, inflammation, cardiovascular disease. However, despite intensive research using strategies, gene knockout (KO) mouse models, about precise roles GPR43 in disease treatment remains inconsistent. Here, we comprehensively review latest findings from functional studies signaling mechanisms underlie activities well highlight multifaceted health We anticipate this knowledge will guide future priorities development effective interventions.

Language: Английский

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Functional expression mechanisms of food-derived components based on target proteins

Bioscience Biotechnology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Food-derived polyphenols and some alkaloids have reported bioactivities related to the prevention of systemic metabolic disorders such as obesity, glucose intolerance, dyslipidemia. For food-derived components exert their functions in vivo, it is essential interact with biological factors proteins, lipids, nucleic acids. However, still unclear whether bioactive foods express target factors. In this review, I introduce proteins which cells.

Language: Английский

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Sulfated and Glucuronidated Conjugates of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid Can Promote NO Production by Elevated Ca²⁺ Release from the Endoplasmic Reticulum in HUVECs

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

We aimed to clarify whether metabolic conjugates of sulfated and glucuronidated forms have the physiological potential produce vasorelaxant nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs), using 3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA), a metabolite dietary flavonoids gut. Treatment HUVECs with HMPAs significantly increased NO production eNOS phosphorylation. A transporter-inhibitor-aided cellular uptake experiment revealed that both were incorporated into via MCT, OATP1A2, GLUT transporters, whereas intact HMPA was transported MCT OATP1A2 routes. Fluo-4-probe Ca2+ assay demonstrated intracellular concentration by stimulating IP3R endoplasmic reticulum CaMKII/eNOS signaling cascade. In conclusion, our knowledge, this study provides first evidence may stimulate HUVECs.

Language: Английский

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Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Regulating Oxidative Stress and Muscle Fiber Composition

Nutrients, Journal Year: 2025, Volume and Issue: 17(4), P. 668 - 668

Published: Feb. 13, 2025

Background/Objectives: Our previous study demonstrated that 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) administration improved grip strength and reduced blood urea nitrogen levels, but its underlying mechanisms remain unclear. This aimed to investigate the effects of HMPA on oxidative stress muscle fiber composition, emphasizing potential role in modulating redox signaling pathways influencing development. Methods: Eight-week-old male C57BL/6 mice were orally administered solution (50 or 500 mg/kg/day) distilled water (10 mL/kg) for 14 days, then divided into sedentary exhaustive exercise groups evaluate status, myosin heavy chain (MHC) isoform expression, mechanisms. Results: Both low high doses by decreasing plasma reactive oxygen metabolites. High-dose nitrite/nitrate levels enhanced antioxidant capacity post-exercise, accompanied changes mRNA abundance enzymes (e.g., Sod1 Nqo1) reductions nitric oxide synthases Nos2 Nos3) soleus. Additionally, high-dose increased protein expression MYH4 soleus, while low-dose gene Myh4 Igf1, suggesting may promote fast-twitch hypertrophy through activation IGF-1 pathway. Furthermore, significantly Sirt1 Nrf1, as well AMPK phosphorylation improve mitochondrial biogenesis adaptation. Conclusions: These findings suggest serve a dietary supplement regulate balance, enhance defenses, formation fibers.

Language: Английский

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Acidipropionibacterium acidipropionici, a propionate-producing bacterium, contributes to GPR41 signaling and metabolic regulation in high-fat diet-induced obesity in mice

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: April 3, 2025

Obesity is a major healthcare problem worldwide and induced by excess energy intake, resulting in gut microbial composition diversity changes. Through fermentation of dietary fibers, short-chain fatty acids (SCFAs) act as host sources signaling molecules via G protein-coupled receptors such GPR41. Acidipropionibacterium acidipropionici widely used many applications; however, vivo studies on the beneficial effect A. propionate production homeostasis are unclear. Therefore, this study aimed to investigate metabolic effects focusing GPR41 high-fat diet (HFD)-induced obesity mouse model. Here, we demonstrated that OB7439 improved metabolism HFD-induced mice. The intake obese mice increasing production, regulating glucose tolerance, inhibiting hepatic inflammation signaling. Our findings shed light potential using an SCFA producer for prevention treatment disorders. Based these results, suggest may be therapeutic bacterium inhibits modulates community.

Language: Английский

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Structure-activity relationship studies of tetrahydroquinolone derivatives as GPR41 modulators

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 107, P. 129758 - 129758

Published: April 17, 2024

Language: Английский

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Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6627 - 6627

Published: June 16, 2024

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, effect HMPA on muscle function remains unknown. This study investigated effects strength exercise endurance capacity. Mice were orally administered low high doses for 14 days subjected to grip force treadmill exhaustion tests evaluate function. Our results showed HMPA-administered groups significantly enhanced absolute (p = 0.0256) relative 0.0209), low-dose decreased plasma level blood urea nitrogen after 0.0183), but did not affect performance. Low-dose administration increased Myf5 expression in sedentary mice 0.0106), suggesting may promote development. Additionally, improved hepatic glucose lipid metabolism, inhibited muscular metabolism protein catabolism, indicated by changes mRNA levels related genes. These findings suggest promising supplement health

Language: Английский

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A critical examination of human data for the biological activity of phenolic acids and their phase-2 conjugates derived from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines

Critical Reviews in Food Science and Nutrition, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 60

Published: Oct. 9, 2024

Free or conjugated aromatic/phenolic acids arise from the diet, endogenous metabolism of catecholamines (adrenaline, noradrenaline, dopamine), protein (phenylalanine, tyrosine), pharmaceuticals (aspirin, metaprolol) plus gut microbiota dietary (poly)phenols and undigested protein. Quantitative data obtained with authentic calibrants for 112 including phase-2 conjugates in human plasma, urine, ileal fluid, feces tissues have been collated mean/median values compared

Language: Английский

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Propionate–producing bacteria, Acidipropionibacterium acidipropionici, prevents metabolic dysregulation via GPR41 signaling in high-fat diet-induced obese mice

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Obesity is a major healthcare problem worldwide and induced by excess energy intake, resulting in gut microbial composition diversity changes. Through fermentation of dietary fibers, short-chain fatty acids (SCFAs) act as host sources signaling molecules via G protein-coupled receptors such GPR41. Acidipropionibacterium acidipropionici widely used many applications; however, vivo studies on the effect A. propionate production regulation homeostasis are unclear. Therefore, this study aimed to investigate beneficial metabolic effects focusing GPR41 high-fat diet (HFD)-induced obesity mouse model. Here, we demonstrated that OB7439 (OB7439) improved metabolism HFD-induced mice. The intake obese mice increasing production, regulating glucose tolerance, inhibiting hepatic inflammation signaling. Our findings shed light potential using an SCFA producer for prevention treatment disorders. Based these results, may serve therapeutic bacteria inhibits modulates community.

Language: Английский

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