Furan fatty acid metabolite CMPF is associated with lower risk of type 2 diabetes, but not chronic kidney disease: a longitudinal population-based cohort study.

BACKGROUND: Furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. OBJECTIVE: We performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. METHODS: In the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. RESULTS: Each standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). CONCLUSIONS: Our findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.

Anti-inflammatory effects of Ganoderma lucidum sterols via attenuation of the p38 MAPK and NF-κB pathways in LPS-induced RAW 264.7 macrophages.

Ganoderma lucidum exhibits pronounced anti-inflammatory effects, polysaccharides and triterpenoids are regarded as major constituents displaying the anti-inflammatory activities, whether sterols contribute to this activity remains unclear. Herein Ganoderma lucidum sterols (GLS) were innovatively isolated by a single-step procedure, the profile of GLS was characterized by HPLC-ELSD and shown similar to that of sterols separated by a traditional method, but much higher in content. Furthermore, GLS inhibited inflammation in macrophages by significantly attenuating LPS-induced cell polarization as well as releases and mRNA expressions of pro-inflammatory mediators NO, TNF-α, IL-1ß and IL-6. Moreover, the anti-inflammatory activity of GLS was mediated by MAPK and NF-κB pathways, GLS suppressed MAPK pathways by blocking phosphorylation of p38 but not ERK and JNK, which is complementary with inhibitory effects of Ganoderma polysaccharides and triterpenes on JNK and ERK, indicating Ganoderma sterols may exert synergistic anti-inflammatory effect with polysaccharides and triterpenes. GLS also inhibited NF-κB pathways by restraining phosphorylation and degradation of IκB-α and blocking phosphorylation of NF-κB p65. Molecular docking confirmed that sterols of GLS were directly bound to active sites of p38 and p65 to suppress their activation. Therefore, our findings suggest GLS as natural and safe anti-inflammatory agents to prevent and treat inflammatory diseases.