CMPF is the main metabolite of furan fatty acids and is a uremic toxin (UT). Under physiological conditions, it is excreted into urine through organic anion transporters [1]. CMPF has a high albumin-binding property, and increasing the serum concentration of competitive binding molecules (such as free fatty acids like oleic acid) may indirectly affect the binding of CMPF to albumin [2]. CMPF is mainly present in the liver, heart, and brain and participates in metabolic pathways related to cholesterol, fatty acids, and lipid synthesis [3].
In vitro, treatment with CMPF (0-400μM; 0-24h) can dose- and time-dependently reduce the GSH levels and the expression of GPX4, FHC, and FLC in HK-2 and NRK49F kidney cells, and increase ROS levels, lipid peroxidation, and intracellular iron concentration [4]. Treatment with CMPF (87μM; 30min) significantly increased the exposure of phosphatidylserine markers of erythrocytes, the level of icCa2+, and the permeability fragility of erythrocytes [5].
In vivo, treatment with CMPF (6mg/kg/day; 2 weeks; i.p.) increased the fasting blood glucose concentration in a high-fat diet (HFD)-induced obesity mouse model, aggravated glucose tolerance impairment, and simultaneously decreased β-cell function and increased ROS levels [6]. Treatment with CMPF (6mg/kg/day; 7 days; i.p.) enhanced the liver lipid clearance rate in the HFD-induced mouse fatty liver model, while inhibiting liver lipid accumulation and insulin resistance [7].
References:
[1] Luce M, Bouchara A, Pastural M, et al. FP322 THE UREMIC TOXIN 3 CARBOXY 4 METHYL 5 PROPYL 2 FURANPROPANOIC ACID (CMPF): PARADOX OF ANEW NUTRITIONAL MARKER IN HAEMODIALYSIS[J]. Nephrology Dialysis Transplantation, 2018, 33(suppl_1): i139-i139.
[2] Lim, C.-F., Stockigt, J.R., Curtis, A.J., et al. A naturally occuring furan fatty acid enhances drug inhibition of thyroxine binding in serum. Metabolism 42(11), 1468-1474 (1993).
[3] Prentice K J, Wendell S G, Liu Y, et al. CMPF, a metabolite formed upon prescription omega-3-acid ethyl ester supplementation, prevents and reverses steatosis[J]. EBioMedicine, 2018, 27: 200-213.
[4] Park J S, Kim D H, Choi H I, et al. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells[J]. Cell Death & Disease, 2023, 14(2): 78.
[5] Van Spitzenbergen B A K, Andrade G B, Dias E S, et al. The uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) may enhance eryptosis and increase erythrocyte osmotic fragility through potential activation of PIEZO1[J]. Nephrology Dialysis Transplantation, 2025, 40(7): 1342-1349.
[6] Liu Y, Prentice K J, Eversley J A, et al. Rapid elevation in CMPF may act as a tipping point in diabetes development[J]. Cell reports, 2016, 14(12): 2889-2900.
[7] Mohan H, Brandt S L, Kim J H, et al. 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) prevents high fat diet‐induced insulin resistance via maintenance of hepatic lipid homeostasis[J]. Diabetes, Obesity and Metabolism, 2019, 21(1): 61-72.