To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy intake, in vivo and in vitro experiments were conducted. Three groups of rats were fed diets with high (HC), normal (NC) and low (LC) caloric content that resulted in different energy intake. In vitro, UMR106 cells were incubated in high (HG, 4.5 g/l) or low glucose (LG, 1 g/l) medium. Additional treatments included phosphorus (P), mannitol, rapamycin and everolimus. Intestinal absorption of P and plasma P concentrations were similar in the three groups of rats. As compared with NC, plasma FGF23 concentrations were increased in HC and decreased in the LC group. A significant correlation between energy intake and plasma FGF23 concentrations was observed. In vitro, mRNA FGF23 was significantly higher in UMR106 cells cultured in HG than in LG. When exposed to high P, mRNA FGF23 increased but only when cells were cultured in HG. Cells incubated with HG and mechanistic target of rapamycin (mTOR) inhibitors expressed low mRNA FGF23, similar to the values obtained in LG. In conclusion, this study shows a direct regulation of FGF23 production by energy availability and demonstrates that the mTOR signaling pathway plays a central role in this regulatory system.

Background Epithelial-to-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) contributes to fibrotic thickening of the peritoneum that develops in patients on peritoneal dialysis (PD). The process is thought to be largely mediated by transforming growth factor-beta (TGF-β). As TGF-β has also been implicated in senescence of HPMCs, we have performed an exploratory study to examine if senescent HPMCs can undergo EMT. Methods Omentum-derived HPMCs were rendered senescent by repeated passages in culture. Features of EMT were assessed by immunostaining and quantitative polymerase chain reaction (qPCR) at various stages of the HPMC lifespan and after treatment with or without TGF-β. The motility of HPMCs was assessed in a scratch wound migration assay. Results Replicative senescence of HPMCs was associated with a gradual increase in the constitutive expression of EMT markers, including increased production of extracellular matrix proteins. However, senescent HPMCs also retained epithelial cell features such as cytokeratin, calretinin, and E-cadherin and showed decreased, rather than increased, motility. In contrast, exposure to TGF-β resulted in an up-regulation of mesenchymal markers and down-regulation of epithelial markers. Such effects of TGF-β occurred both in young and senescent cells, although they were less pronounced in senescence. Conclusions Senescence of HPMCs is associated with spontaneous development of several EMT features. At the same time, senescent HPMCs preserve epithelial cell-like characteristics and are less prone to develop a full EMT phenotype in response to TGF-β. These observations may support the concept of cellular senescence being antagonistically pleiotropic with regard to EMT.

Although the correlation coefficient between body mass index (BMI) and poor lipid profile has been reported, representing a cardiovascular risk, the need to find new early detection markers is real. Waist circumference and markers of atherogenic dyslipidemia are not usually measured in medical review appointments. The present study aimed to investigate the relationship between central adiposity and cardiovascular risk. This was a cross-sectional pilot study of 57 young males (age: 35.9 ± 10.85, BMI: 32.4 ± 6.08) recruited from community settings and allocated to non-obese or obese attending to their waist circumference. Total cholesterol (TC), high-density lipoproteins (HDL-C), and low-density lipoproteins (LDL-C) cholesterol and triglycerides (TG) were measured from plasma samples. Patients with at least 100 cm of waist circumference had significantly increased TC, LDL-C, non-HDL-C, and triglycerides and lower levels of HDL-C. The three atherogenic ratios TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C were all optimal in non-obese patients. LDL-C/HDL-C and TG/HDL-C were significantly higher and over the limit when assessing for atherogenic dyslipidemia. The number of patients at risk for cardiovascular events increases 2.5 folds in obese compared to non-obese. Measurement of waist circumference could be adopted as a simpler valid alternative to BMI for health promotion, to alert those at risk of atherogenic dyslipidemia.

Caloric restriction (CR) is known to have multiple beneficial effects on health and longevity. To study the effect of CR on phosphorus metabolism and vascular calcification (VC), rats were fed normal or restricted calories (67% of normal). The phosphorus content of the diets was adjusted to provide equal phosphorus intake independent of the calories ingested. After 50 days of CR, rats had negative phosphorus balance, lower plasma phosphorus, glucose, triglycerides, and leptin, and higher adiponectin than rats fed normal calories. Uremia was induced by 5/6 nephrectomy (Nx). After Nx, rats were treated with calcitriol (80 ng/kg ip every other day) and high-phosphorus diets (1.2% and 1.8%). No differences in aortic calcium content were observed between rats that ate normal or restricted calories before Nx in either rats that received 1.2% phosphorus (11.5 ± 1.7 vs. 10.9 ± 2.1 mg/g tissue) or in rats that received 1.8% phosphorus (12.5 ± 2.3 vs. 12.0 ± 2.9 mg/g of tissue). However, mortality was significantly increased in rats subjected to CR before Nx in both the 1.2% phosphorus groups (75% vs. 25%, P = 0.019) and 1.8% phosphorus groups (100% vs. 45%, P < 0.001). After calcitriol administration was stopped and phosphorus intake was normalized, VC regressed rapidly, but no significant differences in aortic calcium were detected between rats that ate normal or restricted calories during the regression phase (5.7 ± 2.7 and 5.2 ± 1.5 mg/g tissue). In conclusion, CR did not prevent or ameliorate VC and increased mortality in uremic rats.