Thermoneutrality
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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.
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
- látky proti obezitě * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nepřímá kalorimetrie MeSH
- nízká teplota MeSH
- obezita farmakoterapie MeSH
- omega-3 mastné kyseliny terapeutické užití 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
OBJECTIVES: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, for them, below thermoneutrality, on the electrical coupling protein connexin-43 (Cx43) and pro-fibrotic markers in both heart ventricles of male and female hairless SHR rats compared to the wild SHR. METHODS: Some 6-month-acclimated male and female hairless SHR as well as age- and sex-matched wild SHR were included and compared with the non-hypertensive Wistar strain. The left and right heart ventricles were examined for Cx43 topology, myocardial structure, and the histochemistry of capillaries. The protein levels of Cx43, relevant protein kinases, and extracellular matrix proteins (ECMs) were determined by immunoblotting. MMP-2 activity was assessed via zymography, and susceptibility to malignant arrhythmias was tested ex vivo. RESULTS: Cx43 and its phosphorylated variant pCx43368 were significantly reduced in the left heart ventricles of wild SHR males, while to a lesser extent in the hairless SHR. In contrast, these proteins were not significantly altered in the right heart ventricles of males or in both heart ventricles in females, regardless of the rat strain. Pro-arrhythmic Cx43 topology was detected in the left heart ventricle of wild SHR and to a lesser extent in hairless SHR males. TGFβ protein was significantly increased only in the left ventricle of the wild SHR males. MMP-2 activity was increased in the right ventricle but not in the left ventricles of both males and females, regardless of the rat strain. CONCLUSIONS: The findings indicate that the postnatal acclimation of hairless SHR to ambient temperature hampers the downregulation of Cx43 in the left heart ventricle compared to wild SHR males. The decline of Cx43 was much less pronounced in females and not observed in the right heart ventricles, regardless of the rat strain. It may impact the susceptibility of the heart to malignant arrhythmias.
- MeSH
- aklimatizace MeSH
- down regulace MeSH
- hypertenze * metabolismus MeSH
- konexin 43 * metabolismus genetika MeSH
- krysa rodu rattus MeSH
- potkani inbrední SHR * MeSH
- potkani Wistar MeSH
- srdeční arytmie * metabolismus etiologie MeSH
- srdeční komory * metabolismus MeSH
- teplota * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
