A targeted metabolomics approach was used to identify candidate biomarkers of pre-diabetes. The relevance of the identified metabolites is further corroborated with a protein-metabolite interaction network and gene expression data.

Serum fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor and important for the regulation of inorganic phosphate (Pi) homeostasis. In this study, we examined an acute effect of oral Pi loading on serum FGF23 levels to clarify the role in rapid adjustment of serum Pi level. We performed a randomized, double-blind, crossover study in eight healthy male volunteers. The subjects were alternately served one of three test meals containing different Pi amounts (400 mg (P400), 800 mg (P800), and 1200 mg (P1200)) as lunch at noon. The postprandial changes in serum levels of Pi, Ca, 1,25-dihydroxyvitamin D, intact-parathyroid hormone (iPTH), intact-FGF23 (iFGF23), and urinary excretion of Pi and Ca until 8 h after Pi loading were estimated. Serum Pi levels and urinary Pi excretion significantly increased within 1 h after P400 and P800 intake. Serum iPTH levels at 1-2 and 4-6 h after P1200 intake was significantly higher than those of P400 intake. Serum iFGF23 levels slightly decreased up to 8 h after P400 intake and up to 6 h after P800 intake, but not changed in P1200 intake. Significant increase of iFGF23 was observed at 8 h after P1200 intake compared with both P400 and P800 intake. Additionally, negative association was detected between iFGF23 and serum Pi, whereas positive association was observed between iPTH and serum Pi during the short period. We conclude that oral Pi loading cannot rapidly increase serum FGF23 level. FGF23 may be not associated with rapid adaptation of Pi homeostasis.

Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding.

Awareness of phosphorus intake is important because both phosphorus deficiency and overloading impair bone health and quality of life. Phosphorus consumption is increasing in many countries. Most dietary phosphorus is contained in protein-rich foods such as meat, milk, cheese, poultry, fish, and processed foods that contain phosphate-based additives to improve their consistency and appearance. Elevation of extracellular phosphorus levels causes endothelial dysfunction and medial calcification, which are closely associated with the development of cardiovascular disease (CVD). Long-term excessive phosphorus loading, even if it does not cause hyperphosphatemia, can be a risk factor for CVD. In epidemiological studies, higher levels of phosphorus intake have been associated with reduced blood pressure. Interestingly, when examined further, phosphorus from dairy products, but not from other sources, was usually associated with lower blood pressure. A dietary approach to phosphorus reduction is particularly important to prevent bone impairment and CVD in patients with chronic kidney disease. In order to improve bone health and quality of life in the general population, the impact of phosphorous, including in processed foods, should be considered, and measures to indicate the amount of phosphorous in food products should be implemented.

Objective: This study investigates the effects of a late evening snack (LES), of 200 kcal of rice ball, on energy metabolism in cirrhotic patients. Impaired nutritional metabolism has been associated with cirrhosis, and frequent intake of small meals may prevent early-onset starvation, and maintain nourishment in these patients. Subjects: Twenty-one cirrhotic patients and 26 control subjects (Control) were recruited for this study. Patients were subsequently treated by LES (LC-LES) and by a non-LES regimen (LC-NLES).Method: Resting energy expenditure and respiratory quotient (RQ) were assessed by indirect calorimetry at 0830, 1130 and 1430. Blood glucose and non-esterified fatty acids (NEFA) were measured just before the energy metabolism measurements. The regular diet included three major meals and LES, at 0900, 1200, 1800 and 2100, respectively. The Control and LC-NLES groups received only the major meals, whereas the LC-LES group received three meals plus 200 kcal LES for 7 days. There was no difference in the total energy intake among Control, LC-NLES and LC-LES groups. Results: Respiratory quotient in LC-NLES was significantly lower than that of Control at 0830. Respiratory quotient value in LC-LES significantly elevated from that in LC-NLES. The RQ values did not differ among Control, LC-NLES and LC-LES at 2 h after the meal (1130 and 1430). Non-esterified fatty acids in LC-LES were lower than that in LC-NLES after overnight fasting. Conclusions: The ingestion of a 200 kcal rice ball LES can improve the nutritional metabolism in cirrhotic patients.