Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Strassheim, Derek; Sullivan, Timothy M.; Irwin, David; Gerasimovskaya, Evgenia; Lahm, Tim; Klemm, Dwight J.; Dempsey, Edward C.; Stenmark, Kurt R.; Karoor, Vijaya

doi:10.3390/cells10123347

Cited by 6 publications

(4 citation statements)

References 516 publications

(626 reference statements)

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“…38 Specifically, FFAR2 may be a plausible candidate as it is expressed in MKs and their precursor cells. 39 In summary, our data provide unique insights into the functional role of lipids, diet, and lipid metabolism during MK differentiation, maturation, and platelet production. We have further validated an essential receptor, CD36, as a key mechanism for lipid uptake and identified a CD36 mutation that is a genetic determinant of thrombocytopenia and pathological bleeding.…”

Section: Discussionmentioning

confidence: 82%

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Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Barrachina

Pernes

Becker

et al. 2023

Preprint

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Lipids contribute to hematopoiesis and membrane properties and dynamics, however, little is known about the role of lipids in megakaryopoiesis. Here, a lipidomic analysis of megakaryocyte progenitors, megakaryocytes, and platelets revealed a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake and de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in thrombocytopenia. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production, and that changes in dietary fatty acids may be a novel and viable target to modulate platelet counts.

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Section: Discussionmentioning

confidence: 82%

“…38 Specifically, FFAR 2 may be a plausible candidate as it is expressed in MKs and their precursor cells. 39…”

Section: Discussionmentioning

confidence: 99%

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Barrachina

Pernes

Becker

et al. 2023

Preprint

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“…β-Hydroxybutyric acid is the main component of ketone bodies, and the representative peak of urine is 1,643 cm −1 , which is produced by ketogenic diets. β-Hydroxybutyric acid can not only be used as an energy supply fuel, but also can generate ATP through metabolism, and can also generate cellular signals ( Strassheim et al, 2021 ). This cellular signal may help reduce oxidative stress in animals, which is one of the ways to delay aging ( Park and Kim, 2020 ; Habieb et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis

Kong

Liang

et al. 2023

Front. Chem.

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Objective: The issue of when to start treatment in patients with hyperuricemia (HUA) without gout and chronic kidney disease (CKD) is both important and controversial. In this study, Raman spectroscopy (RS) was used to analyze urine samples, and key genes expressed differentially CKD were identified using bioinformatics. The biological functions and regulatory pathways of these key genes were preliminarily analyzed, and the relationship between them as well as the heterogeneity of the urine components of HUA was evaluated. This study provides new ideas for the rapid evaluation of renal function in patients with HUA and CKD, while providing an important reference for the new treatment strategy of HUA disease.Methods: A physically examined population in 2021 was recruited as the research subjects. There were 10 cases with normal blood uric acid level and 31 cases with asymptomatic HUA diagnosis. The general clinical data were collected and the urine samples were analyzed by Raman spectroscopy. An identification model was also established by using the multidimensional multivariate method of orthogonal partial least squares discriminant analysis (OPLS-DA) model for statistical analysis of the data, key genes associated with CKD were identified using the Gene Expression Omnibus (GEO) database, and key biological pathways associated with renal function damage in CKD patients with HUA were analyzed.Results: The Raman spectra showed significant differences in the levels of uric acid (640 cm−1), urea, creatinine (1,608, 1,706 cm−1), proteins/amino acids (642, 828, 1,556, 1,585, 1,587, 1,596, 1,603, 1,615 cm−1), and ketone body (1,643 cm−1) (p < 0.05). The top 10 differentially expressed genes (DEGs) associated with CKD (ALB, MYC, IL10, FOS, TOP2A, PLG, REN, FGA, CCNA2, and BUB1) were identified. Compared with the differential peak positions analyzed by the OPLS-DA model, it was found that the peak positions of glutathione, tryptophan and tyrosine may be important markers for the diagnosis and progression of CKD.Conclusion: The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes. Patients with HUA may have abnormalities in glutathione, tryptophan, tyrosine, and energy metabolism. The application of Raman spectroscopy to analyze urine samples and interpret the heterogeneity of the internal environment of asymptomatic HUA patients can be combined with the OPLS-DA model to mine the massive clinical and biochemical examination information on HUA patients. The results can also provide a reference for identifying the right time for intervention for uric acid as well as assist the early detection of changes in the internal environment of the body. Finally, this approach provides a useful technical supplement for exploring a low-cost, rapid evaluation and improving the timeliness of screening. Precise intervention of abnormal signal levels of internal environment and energy metabolism may be a potential way to delay renal injury in patients with HUA.

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“…GPCRs, such as GPR41 (FFAR3), GPR43 (FFAR2) OLFR78, and GPR109A, interact with SCFAs such as butyrate, acetate, and propionate with different binding activities. Propionate and acetate activate GPR43 signaling, whereas butyrate and propionate activate GPR41 axis signaling [ 109 ].…”

Section: Therapeutic Strategies For Cs-mediated Inflammation and Meta...mentioning

confidence: 99%

Targeting Lung–Gut Axis for Regulating Pollution Particle–Mediated Inflammation and Metabolic Disorders

Cheng

Chang

Luo

et al. 2023

Cells

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Cigarette smoking (CS) or ambient particulate matter (PM) exposure is a risk factor for metabolic disorders, such as insulin resistance (IR), increased plasma triglycerides, hyperglycemia, and diabetes mellitus (DM); it can also cause gut microbiota dysbiosis. In smokers with metabolic disorders, CS cessation decreases the risks of serious pulmonary events, inflammation, and metabolic disorder. This review included recent studies examining the mechanisms underlying the effects of CS and PM on gut microbiota dysbiosis and metabolic disorder development; one of the potential mechanisms is the disruption of the lung–gut axis, leading to gut microbiota dysbiosis, intestinal dysfunction, systemic inflammation, and metabolic disease. Short-chain fatty acids (SCFAs) are the primary metabolites of gut bacteria, which are derived from the fermentation of dietary fibers. They activate G-protein-coupled receptor (GPCR) signaling, suppress histone deacetylase (HDAC) activity, and inhibit inflammation, facilitating the maintenance of gut health and biofunction. The aforementioned gut microbiota dysbiosis reduces SCFA levels. Treatment targeting SCFA/GPCR signaling may alleviate air pollution–associated inflammation and metabolic disorders, which involve lung–gut axis disruption.

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Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Cited by 6 publications

References 516 publications

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis

Targeting Lung–Gut Axis for Regulating Pollution Particle–Mediated Inflammation and Metabolic Disorders

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