Fenofibrate mildly stimulates browning-associated expression in white adipose tissues of young but not old male rats.

The aim of this study was to examine the effects of the hypolipemic drug fenofibrate (FF) and aging on the expression of factors/enzymes involved in brown adipose tissue (BAT) function and browning of white adipose tissue epididymal (eWAT) and subcutaneous (sWAT) depots. Young-adult and old male Wistar rats were fed standard chow (control) or supplemented with 0.1% or 0.5% FF for 30 days. Tissue samples were analysed for gene expression and protein content, and stained with Oil Red O or hematoxylin and eosin. In BAT of young rats, 0.5% FF increased only Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1 (CITED1) protein content and Fgf21 and Gpr109A mRNA expression. The expression of oxidative metabolism related genes (Pgc1α, Cpt1b, Mcad) decreased after 0.5% FF. In BAT of old rats, FF did not affect UCP1 and CITED1 content and had little effect on gene expression. Oil Red O staining of BAT revealed no changes in lipid droplet area upon treatment in either age group. In eWAT of young rats, 0.1FF elevated UCP1 protein content and Ucp1, Pgc-1α, and Mcad expression, whereas 0.5% FF increased PPARα content and Pgc-1α, Cpt1b, Mcad, and Gpr109A levels. In eWAT of old rats, only 0.1FF increased Pgc1α and Mcad expression. In both age groups median cell area of eWAT adipocytes was reduced after 0.5% FF. In sWAT Ucp1 gene expression was very low and UCP1 protein was undetectable. FF upregulated Ucp1, Cited1, Eva1, and Cpt1b expression in sWAT of young rats, with diminished effects in old rats. In both age groups 0.5% FF increased Fgf21 expression in sWAT. Median cell area of sWAT adipocytes decreased only in young rats treated with 0.5% FF. Our results reveal that fenofibrate differentially affects gene expression in BAT, with diminished effects in old compared to young rats. In WAT of young rats FF modestly stimulates the expression of factors/enzymes involved in lipid oxidative metabolism and browning. Aging reduces both these effects. Gpr109A may present a novel gene target upregulated by FF in BAT and eWAT.

The role of low-calorie diets and intermittent fasting in the treatment of obesity and type-2 diabetes.

Obesity is a condition associated with an increased risk of metabolic disorders, and in particular of type-2 diabetes (T2D). The treatment and prevention of obesity and associated metabolic disorders present great medical challenges. A major therapeutic goal in T2D is to control blood glucose levels, which can be achieved by pharmacological and nonpharmacological measures. The latter include increased physical activity and reduction of body fat mass by limiting dietary caloric content. Low-calorie diets (LCDs) involve a reduction in daily caloric intake by 25% to 30%. LCDs should be individualized depending on the patient's energy requirements, the severity of the obesity, and any accompanying diseases and treatments. Intermittent fasting (IF) involves caloric restriction for one or several days a week, or every day as the prolongation of the overnight fast. The results of recent clinical trials have shown that LCDs and intermittent fasting in patients with obesity (including those with coexisting T2D) can lead to a reduction in body fat mass and metabolic parameter improvements. These beneficial effects arise not only from the loss of body mass, but also from the activation of metabolic pathways specific to fasting conditions. However, the paucity of large-scale randomized controlled trials makes it difficult to prescribe LCDs or IF as reliable, routine methods for successful and stable weight loss.

Cuticle hydrolysis in four medically important fly species by enzymes of the entomopathogenic fungus Conidiobolus coronatus.

Entomopathogenic fungi infect insects via penetration through the cuticle, which varies remarkably in chemical composition across species and life stages. Fungal infection involves the production of enzymes that hydrolyse cuticular proteins, chitin and lipids. Host specificity is associated with fungus-cuticle interactions related to substrate utilization and resistance to host-specific inhibitors. The soil fungus Conidiobolus coronatus (Constantin) (Entomophthorales: Ancylistaceae) shows virulence against susceptible species. The larvae and pupae of Calliphora vicina (Robineau-Desvoidy) (Diptera: Calliphoridae), Calliphora vomitoria (Linnaeus), Lucilia sericata (Meigen) (Diptera: Calliphoridae) and Musca domestica (Linnaeus) (Diptera: Muscidae) are resistant, but adults exposed to C. coronatus quickly perish. Fungus was cultivated for 3 weeks in a minimal medium. Cell-free filtrate, for which activity of elastase, N-acetylglucosaminidase, chitobiosidase and lipase was determined, was used for in vitro hydrolysis of the cuticle from larvae, puparia and adults. Amounts of amino acids, N-glucosamine and fatty acids released were measured after 8 h of incubation. The effectiveness of fungal enzymes was correlated with concentrations of compounds detected in the cuticles of tested insects. Positive correlations suggest compounds used by the fungus as nutrients, whereas negative correlations may indicate compounds responsible for insect resistance. Adult deaths result from the ingestion of conidia or fungal excretions.

Application of microRNAs in diagnosis and treatment of cardiovascular disease.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Innovative, more stringent diagnostic and prognostic biomarkers and effective treatment options are needed to lessen its burden. In recent years, microRNAs have emerged as master regulators of gene expression - they bind to complementary sequences within the mRNAs of their target genes and inhibit their expression by either mRNA degradation or translational repression. microRNAs have been implicated in all major cellular processes, including cell cycle, differentiation and metabolism. Their unique mode of action, fine-tuning gene expression rather than turning genes on/off, and their ability to simultaneously regulate multiple elements of relevant pathways makes them enticing potential biomarkers and therapeutic targets. Indeed, cardiovascular patients have specific patterns of circulating microRNA levels, often early in the disease process. This article provides a systematic overview of the role of microRNAs in the pathophysiology, diagnosis and treatment of CVD.

Short-term calorie restriction and refeeding differently affect lipogenic enzymes in major white adipose tissue depots of young and old rats.

The metabolic effects of short-term calorie restriction (SCR) and subsequent refeeding were compared in different white adipose tissue (WAT) depots of young (5-month old) and old (24-month) male Wistar rats. The animals were subjected to a 40% calorie restricted diet (i.e. 40% lower food supply than of control rats) for 30 days, and then re-fed for 0, 2, or 4 days. WAT samples from perirenal (pWAT), epididymal (eWAT), and subcutaneous (sWAT) depots were analysed for the enzymatic activities of ATP-citrate lyase (ACL), fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PD). The total WAT mass almost doubled in old rats, however, aging did not alter the relative proportions of the major regional fat depots. Serum leptin concentration was prominently higher in old rats, in which SCR resulted in less suppression of leptin level than in young animals, whereas refeeding increased leptin concentration in young, but not old, rats. In young rats refeeding elevated leptin gene expression only in pWAT, while in old rats the expression was induced first in eWAT, and later in pWAT. A prominent age-related decrease of ACL and FAS activities, but not of G6PD activity, was found in all the studied WAT depots. In young control rats, ACL activity was highest in pWAT, FAS activity was similar in all WAT depots, and G6PD activity was lowest in eWAT. In old rats, the enzymatic activities were lower in eWAT than in the other depots. The patterns of response to SCR and refeeding varied by age and WAT location. SCR stimulated ACL activity in pWAT but not in other depots of young rats, while FAS activity in pWAT and sWAT did not change in young and decreased in the old animals. Among the studied depots, pWAT was most responsive to refeeding in both age groups. In conclusion, SCR in old rats, as compared to the young, may be accompanied by reduced 'rebound effect' upon returning to unrestricted diet.

Structural and biochemical characteristics of various white adipose tissue depots.

It is now widely accepted that white adipose tissue (WAT) is not merely a fuel storage organ, but also a key component of metabolic homoeostatic mechanisms. Apart from its major role in lipid and glucose metabolism, adipose tissue is also involved in a wide array of other biological processes. The hormones and adipokines, as well as other biologically active agents released from fat cells, affect many physiological and pathological processes. WAT is neither uniform nor inflexible because it undergoes constant remodelling, adapting the size and number of adipocytes to changes in nutrients' availability and hormonal milieu. Fat depots from different areas of the body display distinct structural and functional properties and have disparate roles in pathology. The two major types of WAT are visceral fat, localized within the abdominal cavity and mediastinum, and subcutaneous fat in the hypodermis. Visceral obesity correlates with increased risk of insulin resistance and cardiovascular diseases, while increase of subcutaneous fat is associated with favourable plasma lipid profiles. Visceral adipocytes show higher lipogenic and lipolytic activities and produce more pro-inflammatory cytokines, while subcutaneous adipocytes are the main source of leptin and adiponectin. Moreover, adipose tissue associated with skeletal muscles (intramyocellular and intermuscular fat) and with the epicardium is believed to provide fuels for skeletal and cardiac muscle contraction. However, increased mass of either epicardial or intermuscular adipose tissue correlates with cardiovascular risk, while the presence of the intramyocellular fat is a risk factor for the development of insulin resistance. This review summarizes results of mainly human studies related to the differential characteristics of various WAT depots.

Precision study of the eta3He system using the dp--> 3Heeta reaction.

The differential and total cross sections for the dp--> 3Heeta reaction have been measured in a high precision high statistics COSY-ANKE experiment near threshold using a continuous beam energy ramp up to an excess energy Q of 11.3 MeV with essentially 100% acceptance. The kinematics allowed the mean value of Q to be determined to about 9 keV. Evidence is found for the effects of higher partial waves for Q >or= 4 MeV. The very rapid rise of the total cross section to its maximum value within 0.5 MeV of threshold implies a very large eta3He scattering length and hence the presence of a quasibound state extremely close to threshold.

Progression of early postnatal retinal pathology in a mouse model of neuronal ceroid lipofuscinosis.

PURPOSE: Accumulation of autofluorescent storage material in the CNS is a hallmark of neuronal ceroid lipofuscinosis (NCL, Batten disease). Since the retina is generally the first CNS target affected in NCL and could serve as a means to assess early disease progression as well as potential therapeutic responses, we followed the course of postnatal retinal pathology in tissues from the CLN8 (mnd) mouse model of NCL. RESULTS: Cytoplasmic inclusions in the retinal ganglion cell (RGC) layer were shown by periodic acid schiff stain by P7. TUNEL measurements of cell death became significant at P21 (P<0.001) with most cell death occurring in the photoreceptor layer. Significant autofluorescence and RGC hypertrophy were evident in mnd mice at P0, prior to eye opening or significant cell death. CONCLUSION: An increased understanding of the timing, location, and characteristic retinal pathologies of Batten disease may lead to diagnostic and therapeutic advances in the clinical setting.

The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice.

Ultrastructural reconstruction of 27 fibrillar plaques in different stages of formation and maturation was undertaken to characterize the development of fibrillar plaques in the brains of human APP(SW) transgenic mice (Tg2576). The study suggests that microglial cells are not engaged in Abeta removal and plaque degradation, but in contrast, are a driving force in plaque formation and development. Fibrillar Abeta deposition at the amyloid pole of microglial cells appears to initiate three types of neuropil response: degeneration of neurons, protective activation of astrocytes, and attraction and activation of microglial cells sustaining plaque growth. Enlargement of neuronal processes and synapses with accumulation of degenerated mitochondria, dense bodies, and Hirano-type bodies is the marker of toxic injury of neurons by fibrillar Abeta. Separation of amyloid cores from neurons and degradation of amyloid cores by cytoplasmic processes of hypertrophic astrocytes suggest the protective and defensive character of astrocytic response to fibrillar Abeta. The growth of cored plaque from a small plaque with one microglial cell with an amyloid star and a few dystrophic neurites to a large plaque formed by several dozen microglial cells seen in old mice is the effect of attraction and activation of microglial cells residing outside of the plaque perimeter. This mechanism of growth of plaques appears to be characteristic of cored plaques in transgenic mice. Other features in mouse microglial cells that are absent in human brain are clusters of vacuoles, probably of lysosomal origin. They evolve into circular cisternae and finally into large vacuoles filled with osmiophilic, amorphous material and bundles of fibrils that are poorly labeled with antibody to Abeta. Microglial cells appear to release large amounts of fibrillar Abeta and accumulate traces of fibrillar Abeta in a lysosomal pathway.

MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson's disease.

We have studied MHC class II antigen expression and lymphocytic infiltration during dopaminergic neurone degeneration produced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP). Microglial activation was observed in the striatum and in the substantia nigra (SN) in this model. We noticed a marked increase of MHC class II antigen expression on microglia and T-cell recruitment in these regions after MPTP treatment. B-lymphocytes were not observed. T-cell infiltration predominantly consisted of CD8+ cells at every time point but CD4+ cells were present too. More than a half of the observed lymphocytes showed strong staining of CD44 antigen. Our findings suggest a possible immune system involvement in the pathological process following MPTP intoxication.

The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse.

In degenerative disorders of the CNS an immune system involvement in the pathological process is postulated. The MPTP model of Parkinson's disease seem to be a good model for studying an inflammation following toxic neurodegeneration. In this model, microglial and astroglial reactions were previously found around impaired neurons. In the present work we showed an immune reaction, including lymphocytic infiltration of CD4+ and CD8+ T cells in the substantia nigra and striatum and elevated MHC class I and II antigens expression on microglia. Many activated lymphocytes were present, showing increased LFA-1 and CD44 antigen expression. We found also that ICAM-1 expression increased on the endothelium and appeared on microglia in the injured regions. Treatment with dexamethasone inhibited T-cell infiltration and MHC class II expression, lessened the glial reaction, and also diminished neuronal impairment. These findings suggest that an immune mechanism may contribute to the neuronal damage following MPTP administration.

[Concentration of attention and learning processes in patients with schizophrenic psychosis. Part I. Attention disorders]. / Procesy koncentracji uwagi i uczenia sie u pacjentów z rozpoznaniem psychozy schizofrenicznej. Czesc I. Zaburzenia uwagi.

Test of the ability to focus attention on the task at hand revealed attention deficits in each group of patients under study. The decision taking time in simple reaction test was longest in schizophrenic patients, significantly longer then in patients with affective disorder. It was also fund that chronic schizophrenics performed relatively better in the vigilance test then patients hospitalized for the first time.

[Concentration of attention and learning processes in patients with schizophrenic psychosis. Part II. Process of acquisition of verbal material]. / Procesy koncentracji uwagi i uczenia sie u pacjentów z rozpoznaniem psychozy schizofrenicznej. Czesc II. Procesy zapamietywania materialu werbalnego.

All examined patient groups did worse in tests of auditory acquisition of new verbal material than healthy controls. Long term schizophrenic patients scored lower in these tests than those hospitalized for the first time.

[Characteristics of early and late onset of schizophrenia]. / Charakterystyka schizofrenii o wczesnym i póznym poczatku.

Two groups of patients derived from paranoid schizophrenia population of Mokotów were compared. The early onset group (before 25th year of age 57 persons) and late onset group (after 40 year of age 48 persons). Characteristics of the course of illness in both groups were compared with respect to productive symptomatology and adaptation. The course of illness was more favorable in the case of late onset psychoses (shorter relapses, longer improvements, fewer hospitalizations, better adaptation). In late schizophrenias the productive symptoms were more often directed towards environment and identity and consistency less frequent. These differences were interpreted as differences in mechanism of personality integration with paranoid syndrome in early and late onset schizophrenia.