• MeSH
• aklimatizace MeSH
• AMP cyklický fyziologie   MeSH
• buněčné dělení účinky léků   MeSH
• DNA biosyntéza   MeSH
• exprese genu účinky léků   MeSH
• geny myc účinky léků   MeSH
• hnědá tuková tkáň * cytologie   fyziologie   účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• nízká teplota MeSH
• noradrenalin * farmakologie   MeSH
• novorozenec MeSH
• proteinkinasa C metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• zvířata MeSH

OBJECTIVE: The possibility to counteract the development of obesity in humans by recruiting brown or brite/beige adipose tissue (and thus UCP1) has attracted much attention. Here we examine if a diet that can activate diet-induced thermogenesis can exploit pre-enhanced amounts of UCP1 to counteract the development of diet-induced obesity. METHODS: To investigate the anti-obesity significance of highly augmented amounts of UCP1 for control of body energy reserves, we physiologically increased total UCP1 amounts by recruitment of brown and brite/beige tissues in mice. We then examined the influence of the augmented UCP1 levels on metabolic parameters when the mice were exposed to a high-fat/high-sucrose diet under thermoneutral conditions. RESULTS: The total UCP1 levels achieved were about 50-fold higher in recruited than in non-recruited mice. Contrary to underlying expectations, in the mice with highly recruited UCP1 and exposed to a high-fat/high-sucrose diet the thermogenic capacity of this UCP1 was completely inactivate. The mice even transiently (in an adipostat-like manner) demonstrated a higher metabolic efficiency and fat gain than did non-recruited mice. This was accomplished without altering energy expenditure or food absorption efficiency. The metabolic efficiency here was indistinguishable from that of mice totally devoid of UCP1. CONCLUSIONS: Although UCP1 protein may be available, it is not inevitably utilized for diet-induced thermogenesis. Thus, although attempts to recruit UCP1 in humans may become successful as such, it is only if constant activation of the UCP1 is also achieved that amelioration of obesity development could be attained.

• MeSH
• béžová tuková tkáň metabolismus   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• energetický metabolismus MeSH
• hnědá tuková tkáň * metabolismus   MeSH
• lidé MeSH
• myši MeSH
• obezita * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• hormony štítné žlázy metabolismus   nedostatek   MeSH
• myši MeSH
• nepřímá kalorimetrie metody   využití   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

Whether active UCP1 can reduce ROS production in brown-fat mitochondria is presently not settled. The issue is of principal significance, as it can be seen as a proof- or disproof-of-principle concerning the ability of any protein to diminish ROS production through membrane depolarization. We therefore undertook a comprehensive investigation of the significance of UCP1 for ROS production, by comparing the ROS production in brown-fat mitochondria isolated from wildtype mice (that display membrane depolarization) or from UCP1(-/-) mice (with a high membrane potential). We tested the significance of UCP1 for glycerol-3-phosphate-supported ROS production by three methods (fluorescent dihydroethidium and the ESR probe PHH for superoxide, and fluorescent Amplex Red for hydrogen peroxide), and followed ROS production also with succinate, acyl-CoA or pyruvate as substrate. We studied the effects of the reverse electron flow inhibitor rotenone, the UCP1 activity inhibitor GDP, and the uncoupler FCCP. We also examined the effect of a physiologically induced increase in UCP1 amount. We noted GDP effects that were not UCP1-related. We conclude that only ROS production supported by exogenously added succinate was affected by the presence of active UCP1; ROS production supported by any other tested substrate (including endogenously generated succinate) was unaffected. This conclusion indicates that UCP1 is not involved in control of ROS production in brown-fat mitochondria. Extrapolation of these data to other tissues would imply that membrane depolarization may not necessarily decrease physiologically relevant ROS production. This article is a part of a Special Issue entitled: 18th European Bioenergetics Conference (Biochim. Biophys. Acta, Volume 1837, Issue 7, July 2014).

• MeSH
• elektronová paramagnetická rezonance MeSH
• glycerolfosfáty farmakologie   MeSH
• guanosindifosfát farmakologie   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• imunoblotting MeSH
• iontové kanály genetika   metabolismus   MeSH
• karbonylkyanid-p-trifluormethoxyfenylhydrazon farmakologie   MeSH
• kyselina jantarová farmakologie   MeSH
• kyselina pyrohroznová farmakologie   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondriální proteiny genetika   metabolismus   MeSH
• mitochondrie účinky léků   metabolismus   fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• nízká teplota MeSH
• peroxid vodíku metabolismus   MeSH
• protonové ionofory farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• spotřeba kyslíku účinky léků   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The possibility to use leptin therapeutically for lowering glucose levels in patients with type 1 diabetes has attracted interest. However, earlier animal models of type 1 diabetes are severely catabolic with very low endogenous leptin levels, unlike most patients with diabetes. Here, we aim to test glucose-lowering effects of leptin in novel, more human-like murine models. We examined the glucose-lowering potential of leptin in diabetic models of two types: streptozotocin-treated mice and mice treated with the insulin receptor antagonist S961. To prevent hypoleptinemia, we used combinations of thermoneutral temperature and high-fat feeding. Leptin fully normalized hyperglycemia in standard chow-fed streptozotocin-treated diabetic mice. However, more humanized physiological conditions (high-fat diets or thermoneutral temperatures) that increased adiposity - and thus also leptin levels - in the diabetic mice abrogated the effects of leptin, i.e., the mice developed leptin resistance also in this respect. The glucose-lowering effect of leptin was not dependent on the presence of the uncoupling protein-1 and was not associated with alterations in plasma insulin, insulin-like growth factor 1, food intake or corticosterone but fully correlated with decreased plasma glucagon levels and gluconeogenesis. An important implication of these observations is that the therapeutic potential of leptin as an additional treatment in patients with type 1 diabetes is probably limited. This is because such patients are treated with insulin and do not display low leptin levels. Thus, the potential for a glucose-lowering effect of leptin would already have been attained with standard insulin therapy, and further effects on blood glucose level through additional leptin cannot be anticipated.

• MeSH
• bílá tuková tkáň metabolismus   MeSH
• diabetes mellitus 1. typu metabolismus   MeSH
• experimentální diabetes mellitus metabolismus   MeSH
• glukagon metabolismus   MeSH
• glukoneogeneze MeSH
• hnědá tuková tkáň metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• kortikosteron metabolismus   MeSH
• krevní glukóza účinky léků   metabolismus   MeSH
• kyselina pyrohroznová metabolismus   MeSH
• leptin metabolismus   farmakologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• peptidy farmakologie   MeSH
• přijímání potravy MeSH
• receptor inzulinu antagonisté a inhibitory   MeSH
• spotřeba kyslíku MeSH
• transkriptom MeSH
• uncoupling protein 1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The adverse effects of air pollutants on the respiratory and cardiovascular systems are unquestionable. However, in recent years, indications of effects beyond these organ systems have become more evident. Traffic-related air pollution has been linked with neurological diseases, exacerbated cognitive dysfunction, and Alzheimer's disease. However, the exact air pollutant compositions and exposure scenarios leading to these adverse health effects are not known. Although several components of air pollution may be at play, recent experimental studies point to a key role of ultrafine particles (UFPs). While the importance of UFPs has been recognized, almost nothing is known about the smallest fraction of UFPs, and only >23 nm emissions are regulated in the EU. Moreover, the role of the semivolatile fraction of the emissions has been neglected. The Transport-Derived Ultrafines and the Brain Effects (TUBE) project will increase knowledge on harmful ultrafine air pollutants, as well as semivolatile compounds related to adverse health effects. By including all the major current combustion and emission control technologies, the TUBE project aims to provide new information on the adverse health effects of current traffic, as well as information for decision makers to develop more effective emission legislation. Most importantly, the TUBE project will include adverse health effects beyond the respiratory system; TUBE will assess how air pollution affects the brain and how air pollution particles might be removed from the brain. The purpose of this report is to describe the TUBE project, its background, and its goals.

• MeSH
• látky znečišťující vzduch * analýza   toxicita   MeSH
• mozek MeSH
• pevné částice analýza   toxicita   MeSH
• velikost částic MeSH
• znečištění ovzduší * analýza   statistika a číselné údaje   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• tisková chyba MeSH

To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

• MeSH
• analýza jednotlivých buněk MeSH
• buňky klasifikace   MeSH
• lidé MeSH
• neokortex cytologie   MeSH
• neuroglie klasifikace   MeSH
• neurony klasifikace   MeSH
• terminologie jako téma MeSH
• transkriptom * MeSH
• výpočetní biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH