Pectin and high-amylose maize starch increase caecal hydrogen production and relieve hepatic ischaemia-reperfusion injury in rats.

We investigated whether the feeding of high H2-generating dietary fibre and resistant starch (RS) could suppress hepatic ischaemia-reperfusion (IR) injury, which results from oxidative stress, in rats fed a pectin (Pec) or high-amylose maize starch (HAS) diet. Male Sprague-Dawley rats were fed a control (C) diet, with or without Pec (0-5 % Pec) or HAS (0-30 % HAS) supplementation for 7 d. Portal H2 concentration showed a significant dose-dependent increase with the amount of Pec or HAS supplementation. Plasma alanine and aspartate aminotransferase activities remarkably increased in the C rats (5 % cellulose) due to IR treatment, while it decreased significantly or showed tendencies to decrease in 5 % Pec and 20 % HAS diet-fed rats. The hepatic oxidised glutathione (GSSG):total glutathione ratio increased significantly in IR rats maintained on the C diet compared with sham-operated rats. On the other hand, reduced glutathione (GSH):total glutathione and GSH:GSSG ratios decreased significantly. The GSSG:total glutathione ratio that increased due to IR treatment decreased significantly on HAS and Pec intake, while GSH:total glutathione and GSH:GSSG ratios increased significantly. Hepatic sinusoids of IR rats fed the C diet were occluded, but those of IR rats fed the Pec diet were similar to those in the sham-operated rats. In conclusion, we found that Pec or HAS, which enhance H2 generation in the large intestine, alleviated hepatic IR injury. The present study demonstrates another physiological significance of dietary fibre and RS.We investigated whether the feeding of high H2-generating dietary fibre and resistant starch (RS) could suppress hepatic ischaemia-reperfusion (IR) injury, which results from oxidative stress, in rats fed a pectin (Pec) or high-amylose maize starch (HAS) diet. Male Sprague-Dawley rats were fed a control (C) diet, with or without Pec (0-5 % Pec) or HAS (0-30 % HAS) supplementation for 7 d. Portal H2 concentration showed a significant dose-dependent increase with the amount of Pec or HAS supplementation. Plasma alanine and aspartate aminotransferase activities remarkably increased in the C rats (5 % cellulose) due to IR treatment, while it decreased significantly or showed tendencies to decrease in 5 % Pec and 20 % HAS diet-fed rats. The hepatic oxidised glutathione (GSSG):total glutathione ratio increased significantly in IR rats maintained on the C diet compared with sham-operated rats. On the other hand, reduced glutathione (GSH):total glutathione and GSH:GSSG ratios decreased significantly. The GSSG:total glutathione ratio that increased due to IR treatment decreased significantly on HAS and Pec intake, while GSH:total glutathione and GSH:GSSG ratios increased significantly. Hepatic sinusoids of IR rats fed the C diet were occluded, but those of IR rats fed the Pec diet were similar to those in the sham-operated rats. In conclusion, we found that Pec or HAS, which enhance H2 generation in the large intestine, alleviated hepatic IR injury. The present study demonstrates another physiological significance of dietary fibre and RS

Prevalence of Masked Obesity Associated with Lifestyle-Related Habits, Dietary Habits, and Energy Metabolism in Japanese Young Women

We investigated the prevalence of Masked Obesity (MO) and the correlations between MO and lifestylerelated habits (e.g., exercise habits, dieting habits), dietary habits, energy metabolism, and seasons. The subjects were 131 young Japanese college students. Body composition was measured by bioelectrical impedance method and Resting Metabolic Rate (RMR) was measured by an indirect calorimeter. Subjects with a BMI in the normal range (n=110) were divided into the MO (percentage of body fat to Body Weight [BF]≥30%) and control (C) (BF<30%) groups. Dietary energy and nutrient intakes were calculated from weighed dietary records. A questionnaire on lifestyle habits was obtained individually from the subjects. The percentage of MO was 32% of subjects within normal BMI. The prevalence of MO was the highest in winter, probably due to accumulation of body fat as an adaptation to cold. The MO group had low Fat-Free Mass (FFM) and high BF. RMR of the MO group was significantly lower than that of the C group. The MO group tended to have poor exercise habits, more dieting (restricting calorie intake) experiences and consumed a diet with less vegetables and beans. We concluded that the prevalence of MO was 32%; it was the highest in winter for subjects who had high fat and low FFM. This fact may be due to poor exercise, more dieting experiences and insufficient intake of vegetables and beans. Furthermore, this accumulation of body fat may be partly due to low RMR

Detection of Necroptosis in Ligand-Mediated and Hypoxia-Induced Injury of Hepatocytes Using a Novel Optic Probe-Detecting Receptor-Interacting Protein (RIP)1/RIP3 Binding

Liver injury is often observed in various pathological conditions including posthepatectomy state and cancer chemotherapy. It occurs mainly as a consequence of the combined necrotic and apoptotic types of cell death. In order to study liver/hepatocyte injury by the necrotic type of cell death, we studied signal-regulated necrosis (necroptosis) by developing a new optic probe for detecting receptor-interacting protein kinase 1(RIP)/RIP3 binding, an essential process for necroptosis induction. In the mouse hepatocyte cell line, TIB-73 cells, TNF-alpha/cycloheximide (T/C) induced RIP1/3 binding only when caspase activity was suppressed by the caspase-specific inhibitor z-VAD-fmk (zVAD). T/C/zVAD-induced RIP1/3 binding was inhibited by necrostatin-1 (Nec-1), an allosteric inhibitor of RIP1. The reduced cell survival by T/C/zVAD was improved by Nec-1. These facts indicate that T/C induces necroptosis of hepatocytes when the apoptotic pathway is inhibited/unavailable. FasL also induced cell death, which was only partially inhibited by zVAD, indicating the possible involvement of necroptosis rather than apoptosis. FasL activated caspase 3 and, similarly, induced RIP1/3 binding when the caspases were inactivated. Interestingly. FasL-induced RIP1/3 binding was significantly suppressed by the antioxidants Trolox and N-acetyl cysteine (NAC), suggesting the involvement of reactive oxygen species (ROS) in FasL-induced necroptotic cellular processes. H2O2 . by itself. induced RIP1/3 binding that was suppressed by Nec-1. but not by zVAD. Hypoxia induced RIP1/3 binding after reoxygenation, which was suppressed by Nec-1 or by the antioxidants. Cell death induced by hypoxia/ reoxygenation (H/R) was also improved by Nec-1. Similar to H2O2 , H/R did not require caspase inhibition for RIP1/3 binding, suggesting the involvement of a caspase-independent mechanism for non-ligand-induced and/or redox-mediated necroptosis. These data indicate that ROS can induce necroptosis and mediate the FasL- and hypoxia-induced necroptosis via a molecular mechanism that differs from a conventional caspase-dependent pathway. In conclusion. necroptosis is potentially involved in liver/hepatocyte injury induced by oxidative stress and FasL in the absence of apoptosis

Photo-Activatable Akt Probe: A New Tool to Study the Akt-Dependent Physiopathology of Cancer Cells

Akt is commonly overexpressed and activated in cancer cells and plays a pivotal role in cell survival, protection, and chemoresistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anticancer drugs. Here we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic helix-loop-helix (CIB1), can regulate Akt-associated cell functions. By illuminating blue light to the cells stably transfected with PA-Akt probe, CRY2-Akt (a fusion protein of CRY2 and Akt) underwent a structural change and interacted with Myr-CIBN (myristoylated N-terminal portion of CIB1), anchoring it at the cell membrane. Western blot analysis revealed that 5473 and T308 of the Akt of probe-Akt were sequentially phosphorylated by intermittent and continuous light illumination. Endogenous Akt and GSK-3 beta, one of the main downstream signals of Akt, were also phosphorylated, depending on light intensity. These facts indicate that photo-activation of probe-Akt can activate endogenous Akt and its downstream signals. The photo-activated Akt conferred protection against nutritional deprivation and H2O2 stresses to the cells significantly. Using the newly developed PA-Akt probe. endogenous Akt was activated easily, transiently, and repeatedly. This probe will be a unique tool in studying Akt-associated specific cellular functions in cancer cells and developing anticancer drugs

Non-thermal emissions from a head-tail radio galaxy in 3D magnetohydrodynamic simulations

We present magnetohydrodynamic simulations of a jet-wind interaction in a galaxy cluster and the radio to gamma-ray and the neutrino emissions from this "head-tail galaxy". Our simulation follows the evolution of cosmic-ray (CR) particle spectra with energy losses and the stochastic turbulence acceleration. We find that the reacceleration is essential to explain the observed radio properties of head-tail galaxies, in which the radio flux and spectral index do not drastically change. Our models suggest that hard X-ray emissions can be detected around the head-tail galaxy in the Perseus cluster by the hard X-ray satellites, such as FORCE, and it will potentially constrain the acceleration efficiency. We also explore the origin of the collimated synchrotron threads, which are found in some head-tail galaxies by recent high-quality radio observations. Thin and elongated flux tubes, connecting the two tails, are formed by strong backflows at an early phase. We find that these threads advect with the wind for over 300 Myr without disrupting. The radio flux from the flux tubes is much lower than the typical observed flux. An efficient CR diffusion process along the flux tubes, however, may solve this discrepancy.Comment: 16 pages, 10 figures, accepted for publication in Ap

KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion during the Early Stage of Adipocyte Differentiation

KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE), a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling