Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis

Background Fatty acid metabolism is reportedly associated with various cancers. However, the role of pretreatment serum free fatty acid (FFA) levels in diffuse large B-cell lymphoma (DLBCL) prognosis is still unclear, and our study aimed to better elucidate its influence on clinical outcomes. Methods The medical records of 221 newly diagnosed DLBCL patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2016 were analysed retrospectively. Receiver operating characteristic curve analysis was used to determine a cut-off value for pretreatment serum FFA levels for prognostic prediction in DLBCL patients. The relationship between pretreatment serum FFA levels and clinical and laboratory parameters was analysed. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Results Newly diagnosed DLBCL patients with high pretreatment serum FFA levels (≥0.495 mmol/l) had more B symptoms, higher serum lactate dehydrogenase levels (> upper limit of normal), >1 extranodal site, and higher International Prognostic Index score (3–5) compared to those with low pretreatment serum FFA levels (<0.495 mmol/l). Higher serum FFA levels were independent prognostic factors for poor OS, but not PFS. Conclusions High pretreatment serum FFA levels are associated with lower survival in untreated DLBCL patients.

Kursi Wufarikun Ziyabit Improves the Physiological Changes by Regulating Endoplasmic Reticulum Stress in the Type 2 Diabetes db/db Mice

Kursi Wufarikun Ziyabit (KWZ) is a classic traditional medicine used for the prevention treatment of diabetes in China. It was widely used as healthcare tea in folk and can prevent and treat type 2 diabetes. However, the underlying mechanism of KWZ in type 2 diabetes has not been investigated extensively. Here, the weekly body weight and blood glucose level of KWZ in type 2 diabetes db/db male mice were observed. After 4 weeks of treatment, the physiological changes and pharmacological effects of KWZ were investigated. The results showed that KWZ can significantly decrease fasting blood glucose and improve glucose tolerance and insulin sensitivity in db/db mice. The serum/liver lipid profiles such as LDL-C, TC, TG, and serum-free fatty acid/Fructosamine levels were decreased, and the serum/liver HDL-C levels were increased. In addition, significant improvement in glucose metabolism enzymes and antioxidant enzymes in experimental mice’s livers was observed. Moreover, the expression of GRP78, p-IRE1α/IRE1α, p-eIF2α/eIF2α, and XBP1s was decreased. The expression of p-PERK/PERK, p-Akt/Akt, and p-GSK-3β/GSK-3β was markedly increased. These results suggested that KWZ is effective for type 2 diabetes by improving endoplasmic reticulum (ER) stress in the liver of db/db mice, and it might prevent the damage of insulin Beta cells and alleviate insulin resistance.

Serum free fatty acids are associated with severe coronary artery calcification, especially in diabetes: a retrospective study

Background Serum free fatty acid (FFA) concentrations are associated with coronary heart disease and diabetes mellitus (DM). Few studies focused on the relationship between serum FFA levels and coronary artery calcification (CAC). Methods This was a retrospective, single-centered study recruiting patients underwent FFA quantification, coronary angiography and intravascular ultrasound (IVUS). CAC severity was assessed with the maximum calcific angle (arc) of the calcified plaque scanned by IVUS. Patients with an arc ≥ 180° were classified into the severe CAC (SCAC) group, and those with an arc < 180° were classified into the non-SCAC group. Clinical characteristics, serum indices were compared between 2 groups. Logistic regression, receiver operating characteristic (ROC) curves and area under the curves (AUC) were performed. Results Totally, 426 patients with coronary artery disease were consecutively included. Serum FFA levels were significantly higher in the SCAC group than non-SCAC group (6.62 ± 2.17 vs. 5.13 ± 1.73 mmol/dl, p < 0.001). Logistic regression revealed that serum FFAs were independently associated with SCAC after adjusting for confounding factors in the whole cohort (OR 1.414, CI 1.237–1.617, p < 0.001), the non-DM group (OR 1.273, CI 1.087–1.492, p = 0.003) and the DM group (OR 1.939, CI 1.388–2.710, p < 0.001). ROC analysis revealed a serum FFA AUC of 0.695 (CI 0.641–0.750, p < 0.001) in the whole population. The diagnostic predictability was augmented (AUC = 0.775, CI 0.690–0.859, p < 0.001) in the DM group and decreased (AUC = 0.649, CI 0.580–0.718, p < 0.001) in the non-DM group. Conclusions Serum FFA levels were independently associated with SCAC, and could have some predictive capacity for SCAC. The association was strongest in the DM group.

Insulin-Mediated Substrate Utilization in Women with the Different Phenotypes of PCOS: Role of Androgens

Context/Objective Few studies have explored in vivo insulin action on substrate utilization in women with PCOS. In particular, no data are available in women with different PCOS phenotypes. The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, non-oxidative glucose metabolism (Gnonox), and serum free fatty acid (FFA) in different PCOS phenotypes. Subjects One hundred and eighty-seven non-diabetic women with PCOS, diagnosed according to the Rotterdam criteria. Data from a historical sample of 20 healthy women were used as reference values. Design Whole body substrate utilization data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. Results During hyperinsulinemia, the increase of Gox (Δ Gox), Gnonox, as well as the suppression of Lox (Δ Lox) and serum FFA (Δ% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Δ% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and Δ Gox was lower in women with the classic than in those with the ovulatory phenotype. In multivariate analysis fat mass and free testosterone were independent predictors of Δ Gox, Gnonox and Δ% FFA, whereas only fat mass predicted Δ Lox. Conclusions In women with PCOS, regardless of their phenotypes, insulin-mediated substrate utilization is impaired. This phenomenon is greater in subjects with the classic phenotype. Free testosterone plays an independent role on insulin action abnormalities on glucose and lipid metabolism.

Effects of maternal vitamin D3 during pregnancy on FASN and LIPE mRNA expression in offspring pigs

In this study, sows were fed 200 (LD), 800 (ND) and 3200 (HD) IU of vitamin D3/kg basal diet during pregnancy (from 41 d to birth), respectively. All their offspring pigs were fed the same vitamin D3 replete die. At 150 days of age, a total of 18 offspring pigs (six offspring pigs per maternal diet group, sex balance) were weighed and slaughtered to investigate effects of maternal vitamin D3 during pregnancy on fatty acids synthase (FASN) and hormone-sensitive lipase (LIPE) expression in offspring pigs. The results showed that LD offspring pigs had higher FASN mRNA expression and the ratio of FASN/LIPE mRNA expression in subcutaneous adipose tissue, as well as higher LIPE mRNA expression of longissimus dorsal muscle, whereas, had lower the ratio of FASN/LIPE mRNA expression in longissimus dorsal muscle compared with ND or HD offspring pigs, respectively. Meanwhile, LD offspring pigs had higher carcass fat, average backfat thickness (ABFT), serum insulin and leptin levels, lower intramuscular fat (IMF), serum free fatty acid and triglycerol levels compared with ND or HD offspring pigs. In addition, the ratio of FASN/LIPE mRNA expression was negatively correlated with IMF content, and positively correlated to carcass fat content and ABFT in offspring pigs. Meanwhile, FASN mRNA expression was positively correlated with carcass fat content, while negatively correlated with ABFT in offspring pigs. These results suggested that maternal vitamin D3 affected fat accumulation and meat quality by regulating FASN and LIPE mRNA expression in offspring pigs.