INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) can progress to more severe stages, such as steatohepatitis and fibrosis. Thermoneutral housing together with high-fat diet promoted NAFLD progression in C57BL/6J mice. Due to possible differences in steatohepatitis development between different C57BL/6 substrains, we examined how thermoneutrality affects NAFLD progression in C57BL/6N mice. METHODS: Male mice were fed standard or high-fat diet for 24 weeks and housed under standard (22°C) or thermoneutral (30°C) conditions. RESULTS: High-fat feeding promoted weight gain and hepatic steatosis, but the effect of thermoneutral environment was not evident. Liver expression of inflammatory markers was increased, with a modest and inconsistent effect of thermoneutral housing; however, histological scores of inflammation and fibrosis were generally low (<1.0), regardless of ambient temperature. In standard diet-fed mice, thermoneutrality increased weight gain, adiposity, and hepatic steatosis, accompanied by elevated de novo lipogenesis and changes in liver metabolome characterized by complex decreases in phospholipids and metabolites involved in urea cycle and oxidative stress defense. CONCLUSION: Thermoneutrality appears to promote NAFLD-associated phenotypes depending on the C57BL/6 substrain and/or the amount of dietary fat.

• MeSH
• bydlení MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• hmotnostní přírůstek MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.

• MeSH
• bydlení zvířat MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• Euphausiacea MeSH
• fosfolipidy farmakologie   MeSH
• fyziologie výživy zvířat MeSH
• inzulinová rezistence MeSH
• játra metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater etiologie   terapie   MeSH
• obezita etiologie   terapie   MeSH
• potravní doplňky * MeSH
• rybí oleje farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: During routine haemodialysis (HD) body temperature increases, which contributes to haemodynamic instability. The relative roles of increased heat production and/or incomplete heat transfer are not fully elucidated. Concomitant measurement of heat production and heat transfer may help to assess the factors determining thermal balance during HD.

• MeSH
• bazální metabolismus MeSH
• dialýza ledvin metody   MeSH
• financování organizované MeSH
• lidé středního věku MeSH
• lidé MeSH
• tělesná teplota fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2fl/fl × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process. RESULTS: Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl × Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes. CONCLUSIONS: We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 °C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.

• MeSH
• bílá tuková tkáň cytologie   metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• energetický metabolismus účinky léků   MeSH
• hnědá tuková tkáň cytologie   metabolismus   MeSH
• inzulinová rezistence * MeSH
• lipidová tělíska metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové proteiny genetika   metabolismus   MeSH
• obezita metabolismus   MeSH
• porucha glukózové tolerance metabolismus   MeSH
• termogeneze genetika   MeSH
• tukové buňky cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) exert beneficial effects on health and they could help to prevent development of obesity and associated metabolic disorders. In our previous studies in mice fed high-fat (cHF; ~60 % calories as fat) diet and maintained at 20 °C, dietary LC n-3 PUFA could counteract accretion of body fat, without inducing mitochondrial uncoupling protein 1 (UCP1) in adipose tissue, suggesting that the anti-obesity effect was not linked to adaptive (UCP1-mediated) thermogenesis. To exclude a possible dependence of the anti-obesity effect on any mechanism inducible by cold, experiments were repeated in mice maintained at thermoneutrality (30 °C). Male C57BL/6J mice were fed either cHF diet, or cHF diet supplemented with LC n-3 PUFA, or standard diet for 7 months. Similarly as at 20 °C, the LC n-3 PUFA supplementation reduced accumulation of body fat, preserved lipid and glucose homeostasis, and induced fatty acid re-esterification in epididymal white adipose tissue. Food consumption was not affected by LC n-3 PUFA intake. Our results demonstrated anti-obesity metabolic effect of LC n-3 PUFA, independent of cold-induced thermogenesis and they suggested that induction of fatty acid re-esterification creating a substrate cycle in white fat, which results in energy expenditure, could contribute to the anti-obesity effect.

• MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• glukózový toleranční test MeSH
• homeostáza fyziologie   MeSH
• kyseliny mastné neesterifikované krev   MeSH
• kyseliny mastné omega-3 terapeutické užití   MeSH
• látky proti obezitě * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nepřímá kalorimetrie MeSH
• nízká teplota MeSH
• obezita farmakoterapie   MeSH
• tělesná hmotnost účinky léků   MeSH
• termogeneze účinky léků   fyziologie   MeSH
• triglyceridy krev   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši 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

Uncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1.

• MeSH
• bílá tuková tkáň metabolismus   MeSH
• energetický metabolismus MeSH
• fibroblastové růstové faktory genetika   metabolismus   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• obezita genetika   metabolismus   MeSH
• signální transdukce MeSH
• uncoupling protein 1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Článek předkládá další adaptovaný klinický doporučený postup (KDP), zaměřený na zajišťování a udržování termoneutrálního prostředí v poporodní péči o novorozence, který vznikal podobně (podle ADAPTE protokolu) jako předchozí doporučené postupy uvedené v Pediatrii pro praxi (č. 4/2015, č. 1/2016, č. 4/2017, č. 2 a 5/2018, č. 2/2019). Na základě rešerše byly vyhledány již existující klinické doporučené postupy a jiná doporučení, která byla podrobena metodologické analýze, a poté byl vytvořen návrh nového, adaptovaného doporučeného postupu. Ten byl předložen celkem 398 sestrám z 11 perinatologických center v České republice a na základě jejich připomínek byl vypracován konečný KDP. Cílem postupu je poskytnout kompetentním zdravotnickým pracovníkům praktické informace, týkající se zajišťování normální tělesné teploty novorozence po porodu, v průběhu resuscitace, při transportu, příjmu na oddělení a při první koupeli. Součástí článku jsou informace o měření tělesné teploty u novorozenců a identifikace hypotermie nebo hypertermie.

The article presents another adapted clinical practice guideline (CPG) focused on provision and maintaining of thermoneutral environment in postnatal care of newborn babies, which was developed in a similar way (using the ADAPTE protocol) as the clinical practice guideline published in Pediatrie pro praxi (No. 4/2015, No. 1/2016, No. 4/2017, No. 2 and 5/2018, No. 2/2019). On the basis of a literature search the existing clinical practice guidelines and other recommendations were identified and analyzed methodologically and then a draft of a new, adapted clinical practice guideline was developed. It was presented to 398 nurses from 11 perinatology centres in the Czech Republic and the final CPG was created on the basis of their comments. The aim of the guideline is to give the competent health care workers practical information about ensuring of normal body temperature of the newborn baby after the birth, during resuscitation, transportation, admission to the department and during the first bath. The article also contains information about body temperature measurement in newborn babies and about identification of hypo- and hyperthermia.

• MeSH
• horečka prevence a kontrola   terapie   MeSH
• hypotermie prevence a kontrola   terapie   MeSH
• kontinuální vzdělávání zdravotních sester MeSH
• lidé MeSH
• novorozenec * MeSH
• ošetřovatelství novorozenců metody   trendy   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• tělesná teplota MeSH
• termometrie * metody   trendy   MeSH
• zdravotní sestry MeSH
• Check Tag
• lidé MeSH
• novorozenec * MeSH

Low resting metabolic rate (RMR) in subterranean rodents used to be considered as a physiological adaptation to cope with stresses of the belowground environment. In African mole-rats (Bathyergidae, Rodentia), RMR was reported to be independent of body mass. This deviation from a general mammalian pattern was considered a precondition for evolution of eusociality, occurring in some bathyergids. We measured metabolic rate and thermoregulation in the silvery mole-rat, Heliophobius argenteocinereus, the only bathyergid genus for which well-supported, comparable data were still missing. Low RMR (154.04 mL O(2) h(-1), which is 82% of the value predicted for a rodent) corresponds to the value expected in a subterranean rodent. Broad range of the thermoneutral zone (25-33 degrees C) and only slightly higher conductance (17.3 mL O(2) h(-1) degrees C(-1), i.e. 112.5% of that predicted for subterranean mammals) indicate that H. argenteocinereus is adapted to lower burrow temperatures rather than to high temperatures. Low RMR in this solitary species, as in other subterranean rodents in general, is probably associated particularly with high energetic cost of foraging. Our results combined with data on other mole-rats show clearly that RMR within the Bathyergidae is mass-dependent.

• MeSH
• bazální metabolismus fyziologie   MeSH
• financování organizované MeSH
• fylogeneze MeSH
• mikroftalmičtí podzemní hlodavci metabolismus   růst a vývoj   MeSH
• odpočinek fyziologie   MeSH
• regresní analýza MeSH
• tělesná hmotnost MeSH
• tělesná teplota MeSH
• zvířata MeSH
• Check Tag
• 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