Recent epidemiological and animal studies have suggested that excess intake of phosphate (Pi) is a risk factor for the progression of chronic kidney disease and its cardiovascular complications. However, little is known about the impact of dietary high Pi intake on the development of metabolic disorders such as obesity and type 2 diabetes. In this study, we investigated the effects of dietary Pi on glucose and lipid metabolism in healthy rats. Male 8-wk-old Sprague-Dawley rats were divided into three groups and given experimental diets containing varying amounts of Pi, i.e., 0.2 [low Pi (LP)], 0.6 [control Pi (CP)], and 1.2% [high Pi (HP)]. After 4 wk, the HP group showed lower visceral fat accumulation compared with other groups, accompanied by a low respiratory exchange ratio (V CO2/V O2) without alteration of locomotive activity. The HP group had lower levels of plasma insulin and nonesterified fatty acids. In addition, the HP group also showed suppressed expression of hepatic lipogenic genes, including sterol regulatory element-binding protein-1c, fatty acid synthase, and acetyl-CoA carboxylase, whereas there was no difference in hepatic fat oxidation among the groups. On the other hand, uncoupling protein (UCP) 1 and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) expression were significantly increased in the brown adipose tissue (BAT) of the HP group. Our data demonstrated that a high-Pi diet can negatively regulate lipid synthesis in the liver and increase mRNA expression related to lipid oxidation and UCP1 in BAT, thereby preventing visceral fat accumulation. Thus, dietary P i is a novel metabolic regulator. dietary phosphate; energy metabolism; brown adipose tissue; visceral fat OBESITY CONTINUES TO BE A MAJOR PUBLIC HEALTH PROBLEM worldwide. Overnutrition and an increased consumption of fast foods are primary factors contributing to this problem. Fast foods or processed foods have high energy density and also frequently contain a large amount of P i as a food additive. Recent epidemiological studies have suggested that a high dietary P i intake can be associated with increased cardiovascular risk and other metabolic disorders.P i is an essential nutrient that significantly affects skeletal formation, energy metabolism, and intracellular signaling (43,45). P i homeostasis is regulated by the absorption of P i in the intestine, bone formation/resorption, and reabsorption of P i in the kidney. The kidney is particularly important in the regulation of P i homeostasis (36, 45). Most P i -regulating factors, such as high/low P i intake, 1,25-dihydroxyvitamin D [1,25(OH) 2 D], parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), can regulate P i reabsorption in the kidney to maintain the P i homeostasis (6, 36, 43).Recent epidemiological and animal studies have suggested that an excessive intake of P i is a risk factor for the progression of chronic kidney disease and the occurrence of cardiovascular complications (8, 45). Excess P i has been independently associated with ...

We established patient-like models of lung cancer metastasis by orthotopically implanting human non-small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small-animal computed tomography (CT) and positron-emission tomography-computed tomography (PET/CT) in these models to non-invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non-small cell lung cancer cell lines, A549, FT821 and PC-9, into SCID mice. These mice were then divided into three groups: Control, cis-diamminedichloroplatinum (II) (CDDP) (7-mg/kg CDDP, single administration intraperitoneally), and erlotinib (25 mg/kg erlotinib/day, oral administration 5 days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC-9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18 FDG-PET/CT and CT imaging non-invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.

No abstract

Our aim in this study was to clarify the effects of respiratory-gated PET in the evaluation of lung cancer according to the (18)F-FDG uptake in an orthotopic transplantation mouse model. We created such a model, and we performed PET/CT. The mice were divided into two groups according to tumor volume: a small-tumor group (<20 mm(3)) and a large-tumor group (>20 mm(3)). We reconstructed the following conditions based on list-mode data: non-gated (3D) images and gated (4D) images, divided based on the respiratory cycle (expiration phase, stable phase, and inspiration phase). We calculated the maximum standardized uptake values (SUVmax) in each phase. We used the % difference [= (4D SUVmax - 3D SUVmax)/3D PET SUVmax × 100 (%)] to evaluate the differences in the 4D SUVmax and 3D SUVmax. The 4D SUVmax values were significantly higher than the 3D SUVmax, regardless of the tumor size. The % difference for the small tumors was greater than that for the large tumors, and it was highest in the stable phase. We conclude that the SUVmax in the stable phase under respiratory-gated PET are the most reliable. The SUVmax observed under non-gated PET are considered to be more frequently underestimated in cases involving small tumors than in those involving large tumors. In the chronologic study evaluating the time course of tumor development, the size of the tumor is small in early stage, and respiratory-gated PET is effective in reducing the underestimation of such tumors caused by respiratory motion.

In terms of the growth rate, the MTV and tumor volume were significantly different (P<0.05). It was found that captopril exerted a potential tumor growth-inhibitory effect; this was because the captopril-administrated group showed low values of MTV, maximum standardized uptake value, total lesion glycolysis, and tumor volume in comparison with the control group.