Adipose tissue inflammation, liver fat and insulin resistance in humans

BACKGROUND: Obesity is closely associated with insulin resistance, which is a pathophysiologic condition contributing to the important co-morbidities of obesity, such as the metabolic syndrome and type 2 diabetes mellitus. In obese subjects, adipose tissue is characterized by inflammation (macrophage infiltration, increased expression insulin resistance genes and decreased expression of insulin sensitivity genes). Increased liver fat, without excessive alcohol consumption, is defined as non-alcoholic fatty liver disease (NAFLD) and also associated with obesity and insulin resistance. It is unknown whether and how insulin resistance is associated with altered expression of adipocytokines (adipose tissue-derived signaling molecules), and whether adipose tissue inflammation and NAFLD coexist independent of obesity. Genetic factors could explain variation in liver fat independent of obesity but the heritability of NAFLD is unknown. AIMS: To determine whether acute regulation of adipocytokine expression by insulin in adipose tissue is altered in obesity. To investigate the relationship between adipose tissue inflammation and liver fat content independent of obesity. To assess the heritability of serum alanine aminotransferase (ALT) activity, a surrogate marker of liver fat. METHODS: 55 healthy normal-weight and obese volunteers were recruited. Subcutaneous adipose tissue biopsies were obtained for measurement of gene expression before and during 6 hours of euglycemic hyperinsulinemia. Liver fat content was measured by proton magnetic resonance spectroscopy, and adipose tissue inflammation was assessed by gene expression, immunohistochemistry and lipidomics analysis. Genetic factors contributing to serum ALT activity were determined in 313 twins by statistical heritability modeling. RESULTS: During insulin infusion the expression of insulin sensitivity genes remains unchanged, while the expression of insulin resistance genes increases in obese/insulin-resistant subjects compared to insulin-sensitive subjects. Adipose tissue inflammation is associated with liver fat content independent of obesity. Adipose tissue of subjects with high liver fat content is characterized infiltrated macrophages and increased expression of inflammatory genes, as well as by increased concentrations of ceramides compared to equally obese subjects with normal liver fat. A significant heritability for serum ALT activity was verified. CONCLUSIONS: Effects of insulin infusion on adipose tissue gene expression in obese/insulin-resistant subjects are not only characterized by hyporesponse of insulin sensitivity genes but also by hyperresponse of insulin resistance and inflammatory genes. This suggests that in obesity, the impaired insulin action contributes or self-perpetuates alterations in adipocytokine expression in adipose tissue. Adipose tissue inflammation is increased in subjects with high liver fat compared to equally obese subjects with normal liver fat content. Concentrations of ceramides, the putative mediators of insulin resistance, are increased in adipose tissue in subjects with high liver fat. Genetic factors contribute significantly to variation in serum ALT activity, a surrogate marker of liver fat. These data imply that adipose tissue inflammation and increased liver fat content are closely interrelated, and determine insulin resistance even independent of obesity.

Defoliation and patchy nutrient return drive grazing effects on plant and soil properties in a dairy cow pasture

Large herbivores can influence plant and soil properties in grassland ecosystems, but especially for belowground biota and processes, the mechanisms that explain these effects are not fully understood. Here, we examine the capability of three grazing mechanisms-plant defoliation, dung and urine return, and physical presence of animals (causing trampling and excreta return in patches)-to explain grazing effects in Phleum pratense-Festuca pratensis dairy cow pasture in Finland. Comparison of control plots and plots grazed by cows showed that grazing maintained original plant-community structure, decreased shoot mass and root N and P concentrations, increased shoot N and P concentrations, and had an inconsistent effect on root mass. Among soil fauna, grazing increased the abundance of fungivorous nematodes and Aporrectodea earthworms and decreased the abundance of detritivorous enchytraeids and Lumbricus earthworms. Grazing also increased soil density and pH but did not affect average soil inorganic-N concentration. To reveal the mechanisms behind these effects, we analyzed results from mowed plots and plots that were both mowed and treated with a dung and urine mixture. This comparison revealed that grazing effects on plant attributes were almost entirely explained by defoliation, with only one partly explained by excreta return. Among belowground attributes, however, the mechanisms were more mixed, with effects explained by defoliation, patchy excreta return, and cow trampling. Average soil inorganic-N concentration was not affected by grazing because it was simultaneously decreased by defoliation and increased by cow presence. Presence of cows created great spatial heterogeneity in soil N availability and abundance of fungivorous nematodes. A greenhouse trial revealed a grazing-induced soil feedback on plant growth, which was explained by patchiness in N availability rather than changes in soil biota. Our results show that grazing effects on plant attributes can be satisfactorily predicted using the effects of defoliation, whereas those on soil fauna and soil N availability need understanding of other mechanisms as well. The results indicate that defoliation-induced changes in plant ecophysiology and the great spatial variation in N availability created by grazers are the two key mechanisms through which large herbivores can control grassland ecosystems.

Analysis of forest soil chemistry and hydrology with a dynamic model ACIDIC.

In this study we analyze how the ion concentrations in forest soil solution are determined by hydrological and biogeochemical processes. A dynamic model ACIDIC was developed, including processes common to dynamic soil acidification models. The model treats up to eight interacting layers and simulates soil hydrology, transpiration, root water and nutrient uptake, cation exchange, dissolution and reactions of Al hydroxides in solution, and the formation of carbonic acid and its dissociation products. It includes also a possibility to a simultaneous use of preferential and matrix flow paths, enabling the throughfall water to enter the deeper soil layers in macropores without first reacting with the upper layers. Three different combinations of routing the throughfall water via macro- and micropores through the soil profile is presented. The large vertical gradient in the observed total charge was simulated succesfully. According to the simulations, gradient is mostly caused by differences in the intensity of water uptake, sulfate adsorption and organic anion retention at the various depths. The temporal variations in Ca and Mg concentrations were simulated fairly well in all soil layers. For H+, Al and K there were much more variation in the observed than in the simulated concentrations. Flow in macropores is a possible explanation for the apparent disequilibrium of the cation exchange for H+ and K, as the solution H+ and K concentrations have great vertical gradients in soil. The amount of exchangeable H+ increased in the O and E horizons and decreased in the Bs1 and Bs2 horizons, the net change in whole soil profile being a decrease. A large part of the decrease of the exchangeable H+ in the illuvial B horizon was caused by sulfate adsorption. The model produces soil water amounts and solution ion concentrations which are comparable to the measured values, and it can be used in both hydrological and chemical studies of soils.

Mammalian Mat1 subunit of Transcription Factor IIH in gene-specific and general transcription

All protein-encoding genes in eukaryotes are transcribed into messenger RNA (mRNA) by RNA Polymerase II (RNAP II), whose activity therefore needs to be tightly controlled. An important and only partially understood level of regulation is the multiple phosphorylations of RNAP II large subunit C-terminal domain (CTD). Sequential phosphorylations regulate transcription initiation and elongation, and recruit factors involved in co-transcriptional processing of mRNA. Based largely on studies in yeast models and in vitro, the kinase activity responsible for the phosphorylation of the serine-5 (Ser5) residues of RNAP II CTD has been attributed to the Mat1/Cdk7/CycH trimer as part of Transcription Factor IIH. However, due to the lack of good mammalian genetic models, the roles of both RNAP II Ser5 phosphorylation as well as TFIIH kinase in transcription have provided ambiguous results and the in vivo kinase of Ser5 has remained elusive. The primary objective of this study was to elucidate the role of mammalian TFIIH, and specifically the Mat1 subunit in CTD phosphorylation and general RNAP II-mediated transcription. The approach utilized the Cre-LoxP system to conditionally delete murine Mat1 in cardiomyocytes and hepatocytes in vivo and and in cell culture models. The results identify the TFIIH kinase as the major mammalian Ser5 kinase and demonstrate its requirement for general transcription, noted by the use of nascent mRNA labeling. Also a role for Mat1 in regulating general mRNA turnover was identified, providing a possible rationale for earlier negative findings. A secondary objective was to identify potential gene- and tissue-specific roles of Mat1 and the TFIIH kinase through the use of tissue-specific Mat1 deletion. Mat1 was found to be required for the transcriptional function of PGC-1 in cardiomyocytes. Transriptional activation of lipogenic SREBP1 target genes following Mat1 deletion in hepatocytes revealed a repressive role for Mat1apparently mediated via co-repressor DMAP1 and the DNA methyltransferase Dnmt1. Finally, Mat1 and Cdk7 were also identified as a negative regulators of adipocyte differentiation through the inhibitory phosphorylation of Peroxisome proliferator-activated receptor (PPAR) γ. Together, these results demonstrate gene- and tissue-specific roles for the Mat1 subunit of TFIIH and open up new therapeutic possibilities in the treatment of diseases such as type II diabetes, hepatosteatosis and obesity.

Snoring and sleep apnea in children

Snoring is a primary and major clinical symptom of upper airway obstruction during sleep. Sleep-disordered breathing ranges from primary snoring to significant partial upper airway obstruction, and obstructive sleep apnea. Adult snoring and obstructive sleep apnea have been extensively studied, whereas less is known about these disorders in children. Snoring and more severe obstructive sleep apnea have been shown to have a harmful effect on the neurobehavioral development of children, but the mechanisms of this effect remains unknown. Furthermore, the correlation of this effect to objective sleep study parameters remains poor. This study evaluated the prevalence of snoring in preschool-aged children in Finland. Host and environmental risk factors, and neurobehavioral and neurocognitive symptoms of children suffering from snoring or obstructive sleep apnea were also investigated. The feasibility of acoustic rhinometry in young children was assessed. The prevalence and risk factors of snoring (I) were evaluated by a questionnaire. The random sample included 2100 children aged 1-6 years living in Helsinki. All 3- to 6-year-old children whose parents reported their child to snore always, often, or sometimes were categorized as snorers, and invited to participate to the clinical study (II-IV). Non-snoring children whose parents were willing to participate in the clinical study were invited to serve as controls. Children underwent a clinical ear-nose-throat examination. Emotional, behavioral, and cognitive performances were evaluated by Child Behavioral Checklist (CBCL), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) and NEPSY-A Developmental Neuropsychological Assessment (NEPSY). Nasal volume was measured by acoustic rhinometry, and nasal resistance by rhinomanometry. Lateral and posteroanterior cephalometry were performed. A standard overnight ambulatory polysomnography was performed in the home environment. Twenty-six healthy children were tested in order to assess the feasibility of acoustic rhinometry in young children (V). Snoring was common in children; 6.3% of children snored always or often, whereas 81.3% snored never or occasionally. No differences were apparent between snorers and non-snorers regarding age, or gender. Pediatric snoring was associated with recurrent upper respiratory infections, otitis media, and allergic rhinitis. Exposure to parental tobacco smoke, especially maternal smoking, was more common among snorers. Rhinitis was more common among children who exposured to tobacco smoke. Overnight polysomnography (PSG) was performed on 87 children; 74% showed no signs of significant upper airway obstruction during sleep. Three children had obstructive apnea/hypopnea index (OAHI) greater than 5/h. Age, gender, or a previous adenoidectomy or tonsillectomy did not correlate with OAHI, whereas tonsillar size did correlate with OAHI. Relative body weight and obesity correlated with none of the PSG parameters. In cephalometry, no clear differences or correlations were found in PSG parameters or between snorers and non-snorers. No correlations were observed between acoustic rhinometry, rhinomanometry, and PSG parameters. Psychiatric symptoms were more frequent in the snoring group than in the nonsnoring group. In particular, anxious and depressed symptoms were more prevalent in the snoring group. Snoring children frequently scored lower in language functions. However, PSG parameters correlated poorly with neurocognitive test results in these children. This study and previous studies indicate that snoring without episodes of obstructive apnea or SpO2 desaturations may cause impairment in behavioral and neurocognitive functions. The mechanism of action remains unknown. Exposure to parental tobacco smoke is more common among snorers than non-snorers, emphasizing the importance of a smoke-free environment. Children tolerated acoustic rhinometry measurements well.

Does the age of fine root carbon indicate the age of fine roots in boreal forests?

To test the reliability of the radiocarbon method for determining root age, we analyzed fine roots (originating from the years 1985 to 1993) from ingrowth cores with known maximum root age (1 to 6 years old). For this purpose, three Scots pine (Pinus sylvestris L.) stands were selected from boreal forests in Finland. We analyzed root 14C age by the radiocarbon method and compared it with the above-mentioned known maximum fine root age. In general, ages determined by the two methods (root 14C age and ingrowth core root maximum age) were in agreement with each other for roots of small diameter (<0.5mm). By contrast, in most of the samples of fine roots of larger diameter (1.5-2mm), the 14C age of root samples of 1987-89 exceeded the ingrowth core root maximum age by 1-10 years. This shows that these roots had received a large amount of older stored carbon from unknown sources in addition to atmospheric CO2 directly from photosynthesis. We conclude that the 14C signature of fine roots, especially those of larger diameter, may not always be indicative of root age, and that further studies are needed concerning the extent of possible root uptake of older carbon and its residence time in roots. Keywords: fine root age, Pinus sylvestris, radiocarbon, root carbon, ingrowth cores, tree ring

Jakojuuriviljelyn vaikutus kasvihuonekurkun (Cucumis sativus L.) kasvuun ja kehitykseen

Kasvit ottavat vettä parhaiten kasteluravinneliuoksesta, jonka ravinnepitoisuus on pieni. Intensiivisessä kasvihuonetuotannossa käytetään silti kastelulannoituksessa usein korkeita ravinnepitoisuuksia ravinnepuutosten ja satotappioiden välttämiseksi. Jakojuuriviljelyssä kasvin juuriston annetaan kasvaa kahteen erilliseen kasvualustaosioon. Tällöin toiselle puolelle annetaan johtokyvyltään väkevää ja toiselle puolelle laimeaa ravinneliuosta. Erityisesti kasvihuonekurkun, joka on herkkä kasvualustan suolaisuuden aiheuttamille vedensaantiongelmille, on todettu hyötyvän tästä tekniikasta, mikä näkyy kasvaneina satoina. Tämän MTT Piikkiössä toteutetun kasvihuonekurkun jakojuuriviljelytutkimuksen tavoitteena oli tarkentaa tekniikkaa erityisesti kasteluliuosten johtokyvyn osalta. Yhtenäisjuuriviljelyn ja perinteisen jakojuuriviljelyn lisäksi kokeessa oli kaksi jakojuuriviljelykäsittelyä, joissa ravinneliuosväkevyyksiä vaihdettiin väliajoin juuriston toimintakyvyn parantamiseksi. Erillisessä osakokeessa tutkittiin erilaisten johtokyky-yhdistelmien vaikutusta kasvihuonekurkun vegetatiiviseen kasvuun maanpäällisten ja -alaisten kasvinosien välillä sekä juurten morfologiaan ja anatomiaan. Tulokset osoittivat, että jakojuuriviljely lisäsi kasvihuonekurkun sadontuottoa jopa 16 %, mutta ei vaikuttanut koko viljelykauden veden tai ravinteiden ottoon. Yhtenäisjuuriviljelyssä muodostui eniten piikkikärkisiä hedelmiä, mikä viittaa vedensaantiongelmiin haihdutustarpeen ollessa suurin. Viljelytekniikalla ei ollut vaikutusta kasvien vegetatiiviseen kasvuun tai kasvuston rakenteeseen. Lehtiruodeista tehdyt nitraatti- ja kaliummittaukset osoittivat, ettei kasteluliuosten ravinnepitoisuuksilla ollut vaikutusta juurten ravinteiden ottoon. Erilaisilla johtokyky-yhdistelmillä oli huomattavampi vaikutus kasvihuonekurkun juurten painoon kuin verson painoon tai varren pituuskasvuun. Lehtiruotianalyysit viittasivat ravinteiden erilaiseen allokointiin eri johtokyky-yhdistelmissä. Korkeiden johtokykyjen aiheuttama osmoottinen stressi johti muutoksiin juurten morfologiassa ja anatomiassa. Tulosten perusteella jakojuuriviljely paransi kehittyvien hedelmien kohdevahvuutta suhteessa muihin kohteisiin vaikuttamatta vegetatiiviseen kasvuun. Kun laimean ja väkevän ravinneliuoksen puolia vaihdettiin, juuristo otti joustavasti vettä ja ravinteita olosuhteiden määräämästä edullisemmasta johtokyvystä, jolloin kasvihuonekurkun viljelyssä saavutettiin merkittävä satoetu. Juuriston jakaminen vaikuttanee kasvien hormoniaineenvaihduntaan ja voi heikentää juuriston kasvua heikentämättä sen toimintakykyä, jolloin yhteyttämistuotteita kohdennetaan tehokkaammin maanpäällisten osien kasvuun.