Peroxisome proliferator-activated receptors (PPARs)-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice

<p>Abstract</p> <p>Background</p> <p>Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway.</p> <p>Methods</p> <p>Mice were fed a diet containing 30 en% beef tallow (B diet) for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet). Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks.</p> <p>Results</p> <p>The F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected.</p> <p>Conclusion</p> <p>These results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.</p

Dose-dependent effects, safety and tolerability of fenugreek in diet-induced metabolic disorders in rats

<p>Abstract</p> <p>Background</p> <p>We previously reported that fenugreek (<it>Trigonella foenum-graecum </it>L.) improved diet-induced metabolic disorders in rats. The purpose of the present study was to examine the dose-dependent effects, safety and tolerability of fenugreek.</p> <p>Methods</p> <p>The diets used in this study were the high-fat high-sucrose diet (HFS; lard 50%kcal, sucrose 25%kcal) as a control (Ctrl group) or the HFS containing 0.25% (VL group), 1.25% (L group), 2.50% (M group), 5.00% (H group) or 12.30% (VH group) fenugreek based on the modified version of the AIN-93G purified diet.</p> <p>Results</p> <p>Fenugreek dose-dependently reduced the hepatic triglyceride and total cholesterol levels. Fenugreek also dose-dependently increased the excretion of cholesterol and total bile acids into the feces. However, the glucose tolerance showed no significant change by fenugreek administration. The VL and L groups did not significantly change triglyceride or total cholesterol levels in the liver. The VL group showed no increase in excretion of triglyceride, total cholesterol or bile acids in the feces. The VH group showed appetite reduction and diarrhea, while no adverse effect or symptoms were observed in the M group.</p> <p>Conclusion</p> <p>These results suggest that fenugreek inhibited lipid accumulation in the liver by increasing the lipid excretion in the feces. The effective, safe and tolerable dose of fenugreek was found to be around 2.50% (w/w).</p

Global Bethe lattice consideration of the spin-1 Ising model

The spin-1 Ising model with bilinear and biquadratic exchange interactions and single-ion crystal field is solved on the Bethe lattice using exact recursion equations. The general procedure of critical properties investigation is discussed and full set of phase diagrams are constructed for both positive and negative biquadratic couplings. In latter case we observe all remarkable features of the model, uncluding doubly-reentrant behavior and ferrimagnetic phase. A comparison with the results of other approximation schemes is done.Comment: Latex, 11 pages, 13 ps figures available upon reques

Absence of re-entrant phase transition of the antiferromagnetic Ising model on the simple cubic lattice: Monte Carlo study of the hard-sphere lattice gas

We perform the Monte Carlo simulations of the hard-sphere lattice gas on the simple cubic lattice with nearest neighbour exclusion. The critical activity is estimated, $z_{\rm c} = 1.0588 \pm 0.0003$. Using a relation between the hard-sphere lattice gas and the antiferromagnetic Ising model in an external magnetic field, we conclude that there is no re-entrant phase transition of the latter on the simple cubic lattice.Comment: 13 pages(4 LaTeX figures included), EDRUSBA-94092

Reentrant Phase Transitions of the Blume-Emery-Griffiths Model for a Simple Cubic Lattice on the Cellular Automaton

The spin-1 Ising (BEG) model with the nearest-neighbour bilinear and biquadratic interactions and single-ion anisotropy is simulated on a cellular automaton which improved from the Creutz cellular automaton(CCA) for a simple cubic lattice. The simulations have been made for several sets of parameters $K/J$ and $D/J$ in the $-3<D/J\leq 0$ and $-1\leq K/J\leq 0$ parameter regions. The re-entrant and double re-entrant phase transitions of the BEG model are determined from the temperature variations of the thermodynamic quantities ($M$, $Q$ and $\chi$). The phase diagrams characterizing phase transitions are compared with those obtained from other methods.Comment: 12 pages 7 figure

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Human aquaporins: regulators of transcellular water flow

Background: Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistentwith their expression in most tissues, AQPs are associatedwith diverse physiological and pathophysiological processes. Scope of review: AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volumeregulation (CVR) is particularly notable. This reviewexamines the regulatory role of AQPs in transcellular water flow, especially in CVR.We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema. Major conclusions: AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapidmovement ofwater across diverse cellmembranes and playing regulatory roles in CVR. Gatingmechanisms have been proposed for human AQPs, but have only been reported for plant andmicrobial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow. General significance: Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins

Adenovirus Gene Transfer to Amelogenesis Imperfecta Ameloblast-Like Cells

To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including “pK7” and/or “RGD” motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3) fiber “knob” domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold) of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both αvβ3/αvβ5 integrins and heparan sulfate proteoglycans (HSPGs) highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease