Circulating 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) levels are associated with hyperglycemia and β cell dysfunction in a Chinese population

Abstract

Several recent clinical studies have suggested that the levels of circulating 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) are significantly higher in patients with gestational diabetes mellitus (GDM), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). This study recruited a total of 516 participants. The following patient populations were enrolled: 99 newly diagnosed cases with T2DM, 219 cases with prediabetes [82 with isolated impaired glucose tolerance (I − IGT), 66 with isolated impaired fasting glucose (I − IFG) and 71 with impaired glucose tolerance and impaired fasting glucose (IGT + IFG)], and 198 cases with normal glucose tolerance [NGT, including 99 first-degree relatives of type 2 diabetes patients (FDRs) and 99 non-FDRs]. We investigated the circulating CMPF levels in subjects with different glucose metabolism statuses and examined the potential link between CMPF and β cell function. Our results indicate that the serum CMPF levels were elevated in the prediabetes, T2DM, and FDRs groups compared to the NGT group. Additionally, the serum CMPF concentrations were independently and negatively associated with the triglyceride levels and Stumvoll first-phase insulin secretion index. Cumulatively, our findings suggest that the circulating CMPF levels can predict glycolipid metabolism disorders. Furthermore, elevated serum CMPF concentrations may determine hyperglycemia and β cell dysfunction.

3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) prevents high fat diet‐induced insulin resistance via maintenance of hepatic lipid homeostasis

“…This observation is in line with the reported beneficial effects of Lovaza on regulation of lipid profiles in humans, suggesting that CMPF may be an active component of FO, contributing to the beneficial metabolic effects seen in humans. Interestingly, human studies have also revealed a strong correlation between elevated circulating CMPF and reduced plasma TG levels, associating CMPF with a role in regulating glycolipid metabolism …”

“…Interestingly, human studies have also revealed a strong correlation between elevated circulating CMPF and reduced plasma TG levels, associating CMPF with a role in regulating glycolipid metabolism. [14][15][16] Mechanistically, CMPF was found to be an inhibitor of acetyl-coA carboxylase (ACC), the master regulator of fatty acid metabolism, as well as having the ability to induce the production of fibroblast growth factor 21 (FGF21). 9 CMPF's long-term preventive effect on HFDinduced hepatic lipid accumulation is absent in FGF21KO mice, suggesting that the long-term beneficial effect of CMPF on metabolism is FGF21 dependent.…”

“…F, Intraperitoneal insulin tolerance test and respective area under the curve (n = 8-14). G, Intraperitoneal glucose tolerance test and respective area under the curve (n =[11][12][13][14]. H, Glucose-stimulated insulin secretion on islets isolated from mice following study completion (n = 8-10).…”

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

“…Furthermore, the same team found that elevated CMPF caused the formation of advanced glycation end‐products, which are known to impair insulin secretion, and increased fatty acid oxidation. This result might explain why CMPF showed an independent negative association with triglycerides in previous studies of individuals with disturbances in carbohydrate metabolism. However, we found that the negative association between CMPF and triglycerides was also present in individuals with NGT in addition to type 2 diabetes mellitus patients.…”

“…In addition, in vitro experiments using human embryonic kidney 293 cells and mouse primary hepatocytes found that CMPF had no intrinsic cytotoxicity in either cell line, and did not inhibit CYP3A4, CYP2D6 or CYP2C9. Furthermore, a study of 516 participants showed an independent and inverse association between CMPF and triglycerides. Cumulatively, these findings show an important role of CMPF as a harmless metabolite involved in the regulation of lipid metabolism, and suggest that it is not cytotoxic to the liver.…”