Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

• MeSH
• adipozita MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň * metabolismus   MeSH
• kyseliny mastné omega-3 * farmakologie   metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• obezita komplikace   prevence a kontrola   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

OBJECTIVE: Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy. METHODS: We used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity. RESULTS: Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly. CONCLUSIONS: Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.

• MeSH
• adrenergní látky metabolismus   MeSH
• hnědá tuková tkáň * metabolismus   MeSH
• inbrední kmeny myší MeSH
• kosterní svaly metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita metabolismus   MeSH
• proteomika * MeSH
• termogeneze fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet. METHODS: Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined. RESULTS: The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis. CONCLUSION: Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases.

• MeSH
• antigen stromálních buněk kostní dřeně metabolismus   farmakologie   MeSH
• glukosa metabolismus   MeSH
• glutamin metabolismus   MeSH
• hypoglykemika farmakologie   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• myši obézní MeSH
• myši MeSH
• obezita farmakoterapie   metabolismus   MeSH
• pioglitazon metabolismus   farmakologie   MeSH
• PPAR gama metabolismus   MeSH
• spirosloučeniny MeSH
• thiazolidindiony * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Impaired thermogenesis observed in mice with whole-body ablation of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β; officially known as PPARGC1B) may result from impaired brown fat (brown adipose tissue; BAT) function, but other mechanism(s) could be involved. Here, using adipose-specific PGC-1β knockout mice (PGC-1β-AT-KO mice) we aimed to learn whether specific PGC-1β ablation in adipocytes is sufficient to drive cold sensitivity. Indeed, we found that warm-adapted (30°C) mutant mice were relatively sensitive to acute cold exposure (6°C). When these mice were subjected to cold exposure for 7 days (7-day-CE), adrenergic stimulation of their metabolism was impaired, despite similar levels of thermogenic uncoupling protein 1 in BAT in PGC-1β-AT-KO and wild-type mice. Gene expression in BAT of mutant mice suggested a compensatory increase in lipid metabolism to counteract the thermogenic defect. Interestingly, a reduced number of contacts between mitochondria and lipid droplets associated with low levels of L-form of optic atrophy 1 was found in BAT of PGC-1β-AT-KO mice. These genotypic differences were observed in warm-adapted mutant mice, but they were partially masked by 7-day-CE. Collectively, our results suggest a role for PGC-1β in controlling BAT lipid metabolism and thermogenesis. This article has an associated First Person interview with the first author of the paper.

• MeSH
• hnědá tuková tkáň * MeSH
• lidé MeSH
• myši MeSH
• PPARGC1A metabolismus   MeSH
• proteiny vázající RNA metabolismus   MeSH
• termogeneze genetika   MeSH
• transkripční faktory * metabolismus   MeSH
• tukové buňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing. METHODS: In this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference. RESULTS: ATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below. CONCLUSION: Our results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• hnědá tuková tkáň * metabolismus   MeSH
• mastné kyseliny metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• termogeneze * MeSH
• triglyceridy metabolismus   MeSH
• uncoupling protein 1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Úvod. De Quervainova choroba je relativně častou příčinou bolesti zápěstí s výskytem zejména v ženské části populace. Rozpoznání choroby je celkem jednoduché, výsledky zejména operační léčby pak výborné a hlavně trvalé, výskyt komplikací léčby je naopak velmi malý. Hlavním problémem je tudíž v diferenciální diagnostice bolestí zápěstí na chorobu pomýšlet. Materiál a metodika Autor zhodnotil v retrospektivní studii založené na vedené dokumentaci soubor provedených ambulantních operací z let 2013–2020. Výsledky. Celkem bylo provedeno ve výše uvedeném období 121 operací (99 žen, 22 mužů), 59 výkonů vpravo, 62 výkonů vlevo, věkové rozhraní od 25 do 91 let, průměrný věk 59,7 let (u žen 56,8 roku, u mužů 62,5 roku). Z komplikací došlo dvakrát k poruše hojení rány (jednou drobná dehiscence, jednou povrchní infekt s minimální sekrecí), jedenkrát k paresteziím v oblasti povrchové větve radiálního nervu. Poruchy hojení byly zvládnuty bez antibiotické terapie pouze formou častějších převazů, parestezie v oblasti povrchové větve radiálního nervu ustaly spontánně bez farmakoterapie či nutnosti revize. Ani jed- nou nebyla pozorována subluxace uvolněných šlach. Diskuze. Ve shodě s literárními údaji v souboru převažují ženy, vyšší věkový průměr je dán strukturou obyvatelstva v regionu. Relativně malý výskyt poškození povrchové větve radiálního nervu lze vysvětlit prováděnou operační technikou založenou na vizualizaci nervu. Závěr. Operační řešení de Quervainovy choroby jednoduchou operační technikou má při správné indikaci výkonu výborné výsledky.

Introduction. De Quervain's disease is relatively common cause of wrist pain, especially in women. Diagnosis of the disease is not difficult, especially the results of operative treatment are very good and most importantly permanent. On the contrary complications rate is very low. The main problem in differential diagnostic of wrist pain is to be aware of the disease. Materials and Methods In retrospective trial 121 outpatient operations conducted from 2013 to 2020 were evaluated, data were extracted from patient's records. Results. The study includes total of 121 operations (99 women, 22 men), 59 operations on right side, 62 operations on left side. Age varied from 25 to 91 years, with average of 59,7 years (56,8 years in women, 62,5 years in men). Complications were 2 times wound healing problems (1 tiny dehiscention, 1 superficial infection), 1 time parestetics of radial sensory nerve, which healed spontaneously without revision operation. Wound healing problems were managed without the use of antibiotics. No tendon subluxation was observed. Discussion. The majority of patients in the study are women, which is in agreement with literature. Higher average age is explainable by population structure in the region, relatively small rate of radial nerve complications is due to provided operative technique using nerve visualisation. Presented results are comparable with data published in literature. The reason for relatively high success rate of the surgeries can be explained by precise diagnostic and routine operative technique. Conclusion. Operative treatment of de Quervain's disease using relatively simply technique provides excellent results.

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

G-protein-coupled receptor GPR10 is expressed in brain areas regulating energy metabolism. In this study, the effects of GPR10 gene deficiency on energy homeostasis in mice of both sexes fed either standard chow or a high-fat diet (HFD) were studied, with a focus on neuronal activation of PrRP neurons, and adipose tissue and liver metabolism. GPR10 deficiency in males upregulated the phasic and tonic activity of PrRP neurons in the nucleus of the solitary tract. GPR10 knockout (KO) males on a standard diet displayed a higher body weight than their wild-type (WT) littermates due to an increase in adipose tissue mass; however, HFD feeding did not cause weight differences between genotypes. Expression of lipogenesis genes was suppressed in the subcutaneous adipose tissue of GPR10 KO males. In contrast, GPR10 KO females did not differ in body weight from their WT controls, but showed elevated expression of lipid metabolism genes in the liver and subcutaneous adipose tissue compared to WT controls. An attenuated non-esterified fatty acids change after glucose load compared to WT controls suggested a defect in insulin-mediated suppression of lipolysis in GPR10 KO females. Indirect calorimetry did not reveal any differences in energy expenditure among groups. In conclusion, deletion of GPR10 gene resulted in changes in lipid metabolism in mice of both sexes, however in different extent. An increase in adipose tissue mass observed in only GPR10 KO males may have been prevented in GPR10 KO females owing to a compensatory increase in the expression of metabolic genes.

• MeSH
• energetický metabolismus genetika   MeSH
• homeostáza genetika   MeSH
• hormon uvolňující prolaktin metabolismus   MeSH
• inzulinová rezistence genetika   MeSH
• metabolismus lipidů genetika   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• obezita genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH