Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoic Acid is Associated with Lipid Profiles and Might Protect Against Non-alcoholic Fatty Liver Disease in Chinese Individuals

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2018 Oct 25

PMID 30353682

Citations 5

Authors

Jiarong Dai

Jufen Yi

Shan Zhang

Peihong Chen

Hua Jin

Xuemei Yu

Xueli Zhang

Affiliations

Soon will be listed here.

Abstract

Aims/introduction: High plasma 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) levels are significantly associated with type 2 diabetes mellitus, which is usually accompanied by metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) with increased triglyceride levels. Thus, we hypothesized that elevated CMPF levels might be related to lipid metabolism and NAFLD risk.

Materials And Methods: Serum CMPF levels were determined using an enzyme-linked immunosorbent assay in a total of 466 individuals, including 116 controls with no NAFLD or type 2 diabetes mellitus, 53 individuals with NAFLD but no type 2 diabetes mellitus, 151 individuals with type 2 diabetes mellitus but no NAFLD, and 146 individuals with both NAFLD and type 2 diabetes mellitus. The associations with age, blood pressure, lipid profiles, body mass index and liver injury marker levels were examined, and a meta-analysis of non-diabetic and diabetic groups was carried out to detect the combined effects.

Results: The CMPF concentration in NAFLD patients was significantly lower than individuals without NAFLD in both the non-diabetic group (P < 0.05) and diabetic group (P < 0.01), and correlated negatively with several parameters of liver function and the adiposity index. Meta-analysis showed that serum CMPF levels was associated with decreased risk of NAFLD after combining the results (odds ratio 0.677, 95% confidence interval 0.552-0.831, P < 0.001). Additionally, the CMPF concentration was independently negatively associated with triglycerides and high-density lipoprotein cholesterol in the meta-analysis. Multiple stepwise regression analysis showed that body mass index, high-density lipoprotein cholesterol, triglyceride level, age, sex and fasting plasma glucose were independently associated with CMPF (all P < 0.05).

Conclusions: The results suggest that serum CMPF levels are negatively related to lipid metabolism and could be used to predict NAFLD development.

Citing Articles

Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

Zarei I, Eloranta A, Klavus A, Vaisto J, Lehtonen M, Mikkonen S iScience. 2024; 27(7):110295.

PMID: 39055945 PMC: 11269805. DOI: 10.1016/j.isci.2024.110295.

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

Dai L, Massy Z, Stenvinkel P, Chesnaye N, Larabi I, Alvarez J Am J Clin Nutr. 2022; 116(6):1842-1851.

PMID: 36166845 PMC: 9761748. DOI: 10.1093/ajcn/nqac278.

Non-invasive evaluation of NAFLD and the contribution of genes: an MRI-PDFF-based cross-sectional study.

Yang A, Zhu X, Zhang L, Zhang Y, Zhang D, Jin M Hepatol Int. 2022; 16(5):1035-1051.

PMID: 35829866 DOI: 10.1007/s12072-022-10355-2.

New perspective on type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease.

Matsuzaka T, Shimano H J Diabetes Investig. 2020; 11(3):532-534.

PMID: 32232972 PMC: 7232277. DOI: 10.1111/jdi.13258.

Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid is associated with lipid profiles and might protect against non-alcoholic fatty liver disease in Chinese individuals.

Dai J, Yi J, Zhang S, Chen P, Jin H, Yu X J Diabetes Investig. 2018; 10(3):793-800.

PMID: 30353682 PMC: 6497611. DOI: 10.1111/jdi.12963.

References

Mabuchi H, Nakahashi H . Inhibition of hepatic glutathione S-transferases by a major endogenous ligand substance present in uremic serum. Nephron. 1988; 49(4):281-3. DOI: 10.1159/000185076. View

Liu Y, Prentice K, Eversley J, Hu C, Batchuluun B, Leavey K . Rapid Elevation in CMPF May Act As a Tipping Point in Diabetes Development. Cell Rep. 2016; 14(12):2889-900. DOI: 10.1016/j.celrep.2016.02.079. View

Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M . Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015; 64(1):73-84. DOI: 10.1002/hep.28431. View

Xu L, Sinclair A, Faiza M, Li D, Han X, Yin H . Furan fatty acids - Beneficial or harmful to health?. Prog Lipid Res. 2017; 68:119-137. DOI: 10.1016/j.plipres.2017.10.002. View

Prentice K, Wendell S, Liu Y, Eversley J, Salvatore S, Mohan H . CMPF, a Metabolite Formed Upon Prescription Omega-3-Acid Ethyl Ester Supplementation, Prevents and Reverses Steatosis. EBioMedicine. 2018; 27:200-213. PMC: 5828468. DOI: 10.1016/j.ebiom.2017.12.019. View

Miyamoto Y, Iwao Y, Mera K, Watanabe H, Kadowaki D, Ishima Y . A uremic toxin, 3-carboxy-4-methyl-5-propyl-2-furanpropionate induces cell damage to proximal tubular cells via the generation of a radical intermediate. Biochem Pharmacol. 2012; 84(9):1207-14. DOI: 10.1016/j.bcp.2012.07.033. View

Niwa T, Aiuchi T, Nakaya K, Emoto Y, Miyazaki T, Maeda K . Inhibition of mitochondrial respiration by furancarboxylic acid accumulated in uremic serum in its albumin-bound and non-dialyzable form. Clin Nephrol. 1993; 39(2):92-6. View

Zhou M, Li Z, Min R, Dong Y, Sun Q, Li Y . Log (TG)/HDL-C ratio as a predictor of decreased islet beta cell function in patients with type 2 diabetes: 6-year cohort study. J Diabetes. 2014; 7(5):689-98. DOI: 10.1111/1753-0407.12229. View

Lankinen M, Hanhineva K, Kolehmainen M, Lehtonen M, Auriola S, Mykkanen H . CMPF does not associate with impaired glucose metabolism in individuals with features of metabolic syndrome. PLoS One. 2015; 10(4):e0124379. PMC: 4398480. DOI: 10.1371/journal.pone.0124379. View

10.

Chalasani N, Younossi Z, Lavine J, Diehl A, Brunt E, Cusi K . The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012; 55(6):2005-23. DOI: 10.1002/hep.25762. View

11.

Dai J, Yi J, Zhang S, Chen P, Jin H, Yu X . Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid is associated with lipid profiles and might protect against non-alcoholic fatty liver disease in Chinese individuals. J Diabetes Investig. 2018; 10(3):793-800. PMC: 6497611. DOI: 10.1111/jdi.12963. View

12.

Niwa T . Removal of protein-bound uraemic toxins by haemodialysis. Blood Purif. 2013; 35 Suppl 2:20-5. DOI: 10.1159/000350843. View

13.

Sun H, Huang Y, Frassetto L, Benet L . Effects of uremic toxins on hepatic uptake and metabolism of erythromycin. Drug Metab Dispos. 2004; 32(11):1239-46. DOI: 10.1124/dmd.104.000521. View

14.

Rroji M, Eloot S, Dhondt A, Van Biesen W, Glorieux G, Neirynck N . Association of advanced age with concentrations of uraemic toxins in CKD. J Nephrol. 2015; 29(1):81-91. DOI: 10.1007/s40620-015-0195-z. View

15.

Younossi Z, Loomba R, Anstee Q, Rinella M, Bugianesi E, Marchesini G . Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology. 2017; 68(1):349-360. PMC: 6511364. DOI: 10.1002/hep.29721. View

16.

Zhang S, Chen P, Jin H, Yi J, Xie X, Yang M . Circulating 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) levels are associated with hyperglycemia and β cell dysfunction in a Chinese population. Sci Rep. 2017; 7(1):3114. PMC: 5465180. DOI: 10.1038/s41598-017-03271-1. View

17.

Mohan H, Brandt S, Kim J, Wong F, Lai M, Prentice K . 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) prevents high fat diet-induced insulin resistance via maintenance of hepatic lipid homeostasis. Diabetes Obes Metab. 2018; 21(1):61-72. DOI: 10.1111/dom.13483. View

18.

Coughlan M, Yap F, Tong D, Andrikopoulos S, Gasser A, Thallas-Bonke V . Advanced glycation end products are direct modulators of β-cell function. Diabetes. 2011; 60(10):2523-32. PMC: 3178291. DOI: 10.2337/db10-1033. View

19.

Savolainen O, Lind M, Bergstrom G, Fagerberg B, Sandberg A, Ross A . Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women. Am J Clin Nutr. 2017; 106(5):1302-1310. DOI: 10.3945/ajcn.117.152850. View

20.

Zheng J, Lin M, Imamura F, Cai W, Wang L, Feng J . Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial. Sci Rep. 2016; 6:29522. PMC: 4941578. DOI: 10.1038/srep29522. View