BMC Physiology最新文献

{"title":"Exercise endurance capacity is markedly reduced due to impaired energy homeostasis during prolonged fasting in FABP4/5 deficient mice.","authors":"Tatsuya Iso,&nbsp;Hikari Haruyama,&nbsp;Hiroaki Sunaga,&nbsp;Miki Matsui,&nbsp;Hiroki Matsui,&nbsp;Rina Tanaka,&nbsp;Yogi Umbarawan,&nbsp;Mas Rizky A A Syamsunarno,&nbsp;Tomoyuki Yokoyama,&nbsp;Masahiko Kurabayashi","doi":"10.1186/s12899-019-0038-6","DOIUrl":"https://doi.org/10.1186/s12899-019-0038-6","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle prefers carbohydrate use to fatty acid (FA) use as exercise intensity increases. In contrast, skeletal muscle minimizes glucose use and relies more on FA during fasting. In mice deficient for FABP4 and FABP5 (double knockout (DKO) mice), FA utilization by red skeletal muscle and the heart is markedly reduced by the impairment of trans-endothelial FA transport, with an increase in glucose use to compensate for reduced FA uptake even during fasting. We attempted to determine whether prolonged fasting affects exercise performance in DKO mice, where constant glucose utilization occurs.</p><p><strong>Results: </strong>A single bout of treadmill exercise was performed in the fed and fasted states. The initial speed was 10 m/min, and gradually increased by 5 m/min every 5 min up to 30 m/min until the mice stopped running. Running distance was significantly reduced by DKO genotype and prior fasting, leading to the shortest distance in fasted DKO mice. Levels of glycogen in skeletal muscle and the liver were nearly depleted in both WT and DKO mice during prolonged fasting prior to exercise. Levels of TG in skeletal muscle were not reduced by exercise in fasted DKO mice, suggesting that intramuscular TG was not utilized during exercise. Hypoglycaemia was accelerated in fasted DKO mice, and this acceleration could be due to constant glucose utilization by red skeletal muscle and the heart where FA uptake is diminished due to defective trans-endothelial FA transport. Taken together, energy supply from serum and storage in skeletal muscle were very low in fasted DKO mice, which could lead to a significant reduction in exercise performance.</p><p><strong>Conclusions: </strong>FABP4/5 have crucial roles in nutrient homeostasis during prolonged fasting for maintaining exercise endurance capacity.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-019-0038-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37227591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation.","authors":"Inka Gallitz,&nbsp;Niklas Lofruthe,&nbsp;Lisa Traeger,&nbsp;Nicole Bäumer,&nbsp;Verena Hoerr,&nbsp;Cornelius Faber,&nbsp;Tanja Kuhlmann,&nbsp;Carsten Müller-Tidow,&nbsp;Andrea U Steinbicker","doi":"10.1186/s12899-018-0037-z","DOIUrl":"https://doi.org/10.1186/s12899-018-0037-z","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72 h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated. The intact, heat-killed bacterium Brucella abortus (BA) was used to analyse its effect on the development of inflammation and hypoferremia in mice with hepatocyte-specific Alk3-deficiency (Alk3^fl/fl; Alb-Cre) compared to control (Alk3^fl/fl) mice.</p><p><strong>Results: </strong>An iron restricted diet prevented development of the iron overload phenotype in mice with hepatocyte-specific Alk3 deficiency. Regular diet leads to iron overload and increased haemoglobin levels in these mice, which protects from the development of AI per se. Fourteen days after BA injection Alk3^fl/fl; Alb-Cre mice presented milder anaemia (Hb 16.7 g/dl to 11.6 g/dl) compared to Alk3^fl/fl control mice (Hb 14.9 g/dl to 8.6 g/dl). BA injection led to an intact inflammatory response in all groups of mice. In Alk3^fl/fl; Alb-Cre mice, SMAD1/5/8 phosphorylation was reduced after BA as well as after infection with Staphylococcus aureus. The reduction of the SMAD1/5/8 signalling pathway due to hepatocyte-specific Alk3 deficiency partly suppressed the induction of STAT3 signalling.</p><p><strong>Conclusion: </strong>The results reveal in vivo, that 1) hepatocyte-specific Alk3 deficiency partly protects from AI, 2) the development of hypoferremia is partly dependent on ALK3, and 3) the ALK3/BMP/hepcidin axis may serve as a possible therapeutic target to attenuate AI.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-018-0037-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35864338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Locomotor activity in fed, fasted, and food-restricted mice lacking tissue-type plasminogen activator.","authors":"Jessica A Krizo,&nbsp;Linley E Moreland,&nbsp;Ashutosh Rastogi,&nbsp;Xiang Mou,&nbsp;Rebecca A Prosser,&nbsp;Eric M Mintz","doi":"10.1186/s12899-018-0036-0","DOIUrl":"https://doi.org/10.1186/s12899-018-0036-0","url":null,"abstract":"<p><strong>Background: </strong>Circadian rhythms of physiology and behavior are driven by a circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This clock is synchronized to environmental day/night cycles by photic input, which is dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from plasminogen by the enzyme tissue-type plasminogen activator (tPA). In this study, we evaluate circadian function in mice lacking functional tPA.</p><p><strong>Results: </strong>tPA^-/- mice have normal circadian periods, but show decreased nocturnal wheel-running activity. This difference is eliminated or reversed on the second day of a 48-h fast. Similarly, when placed on daily cycles of restricted food availability the genotypic difference in total wheel-running activity disappears, and tPA^-/- mice show equivalent amounts of food anticipatory activity to wild type mice.</p><p><strong>Conclusions: </strong>These data suggest that tPA regulates nocturnal wheel-running activity, and that tPA differentially affects SCN-driven nocturnal activity rhythms and activity driven by fasting or temporal food restriction.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-018-0036-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35767614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin expression during early postnatal development of the murine cochlea.","authors":"Takayuki Kudo,&nbsp;Philine Wangemann,&nbsp;Daniel C Marcus","doi":"10.1186/s12899-018-0035-1","DOIUrl":"https://doi.org/10.1186/s12899-018-0035-1","url":null,"abstract":"<p><strong>Background: </strong>Claudins are major components of tight junctions, which form the paracellular barrier between the cochlear luminal and abluminal fluid compartments that supports the large transepithelial voltage difference and the large concentration differences of K⁺, Na⁺ and Ca²⁺ needed for normal cochlear function. Claudins are a family of more than 20 subtypes, but our knowledge about expression and localization of each subtype in the cochlea is limited.</p><p><strong>Results: </strong>We examined by quantitative RT-PCR the expression of the mRNA of 24 claudin isoforms in mouse cochlea during postnatal development and localized the expression in separated fractions of the cochlea. Transcripts of 21 claudin isoforms were detected at all ages, while 3 isoforms (Cldn-16, - 17 and - 18) were not detected. Claudins that increased expression during development include Cldn-9, - 13, - 14, - 15, and -19v2, while Cldn-6 decreased. Those that do not change expression level during postnatal development include Cldn-1, - 2, - 3, - 4, - 5, - 7, - 8, -10v1, -10v2, - 11, - 12, -19v1, - 20, - 22, and - 23. Our investigation revealed unique localization of some claudins. In particular, Cldn-13 expression rapidly increases during early development and is mainly expressed in bone but only minimally in the lateral wall (including stria vascularis) and in the medial region (including the organ of Corti). No statistically significant changes in expression of Cldn-11, - 13, or - 14 were found in the cochlea of Slc26a4 ^-/- mice compared to Slc26a4 ^+/- mice.</p><p><strong>Conclusions: </strong>We demonstrated developmental patterns of claudin isoform transcript expression in the murine cochlea. Most of the claudins were associated with stria vascularis and organ of Corti, tissue fractions rich in tight junctions. However, this study suggests a novel function of Cldn-13 in the cochlea, which may be linked to cochlear bone marrow maturation.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-018-0035-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35765339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin is required for maintaining normal body temperature in a cold environment.","authors":"Qiong Wei,&nbsp;Jong Han Lee,&nbsp;Hongying Wang,&nbsp;Odelia Y N Bongmba,&nbsp;Chia-Shan Wu,&nbsp;Geetali Pradhan,&nbsp;Zilin Sun,&nbsp;Lindsey Chew,&nbsp;Mandeep Bajaj,&nbsp;Lawrence Chan,&nbsp;Robert S Chapkin,&nbsp;Miao-Hsueh Chen,&nbsp;Yuxiang Sun","doi":"10.1186/s12899-017-0034-7","DOIUrl":"https://doi.org/10.1186/s12899-017-0034-7","url":null,"abstract":"<p><strong>Background: </strong>Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we investigated the role of adiponectin in thermogenesis using adiponectin-null mice (Adipoq ^-/-).</p><p><strong>Methods: </strong>Body composition was measured using EchoMRI. Metabolic parameters were determined by indirect calorimetry. Insulin sensitivity was evaluated by glucose- and insulin- tolerance tests. Core body temperature was measured by a TH-8 temperature monitoring system. Gene expression was assessed by real-time PCR and protein levels were analyzed by Western blotting and immunohistochemistry. The mitochondrial density of brown adipose tissue was quantified by calculating the ratio of mtDNA:total nuclear DNA.</p><p><strong>Results: </strong>Under normal housing temperature of 24 °C and ad libitum feeding condition, the body weight, body composition, and metabolic profile of Adipoq ^-/- mice were unchanged. Under fasting condition, Adipoq ^-/- mice exhibited reduced energy expenditure. Conversely, under cold exposure, Adipoq ^-/- mice exhibited reduced body temperature, and the expression of thermogenic regulatory genes was significantly reduced in brown adipose tissue (BAT) and subcutaneous white adipose tissue (WAT). Moreover, we observed that mitochondrial content was reduced in BAT and subcutaneous WAT, and the expression of mitochondrial fusion genes was decreased in BAT of Adipoq ^-/- mice, suggesting that adiponectin ablation diminishes mitochondrial biogenesis and altered mitochondrial dynamics. Our study further revealed that adiponectin deletion suppresses adrenergic activation, and down-regulates β3-adrenergic receptor, insulin signaling, and the AMPK-SIRT1 pathway in BAT.</p><p><strong>Conclusions: </strong>Our findings demonstrate that adiponectin is an essential regulator of thermogenesis, and adiponectin is required for maintaining body temperature under cold exposure.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-017-0034-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35474381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen receptor is expressed in mouse cardiomyocytes at prenatal and early postnatal developmental stages.","authors":"Enrique Pedernera,&nbsp;María José Gómora,&nbsp;Iván Meneses,&nbsp;Marlon De Ita,&nbsp;Carmen Méndez","doi":"10.1186/s12899-017-0033-8","DOIUrl":"https://doi.org/10.1186/s12899-017-0033-8","url":null,"abstract":"<p><strong>Background: </strong>Previous studies show that androgens are involved in hypertrophy and excitability of cardiomyocytes and that their effects are mediated through their receptor. The aim of this study was to evaluate the presence of androgen receptor (AR) in mouse heart during prenatal and early postnatal stages.</p><p><strong>Results: </strong>The expression of AR and related genes, alpha myosin heavy chain -Myh6-, beta myosin heavy chain -Myh7- and atrial natriuretic factor -Nppa- was simultaneously evaluated by semiquantitative RT-PCR. AR was also detected by immunohistochemistry. Androgen receptor mRNA was detected in hearts from 10.5 days post coitum to 16 postnatal days. A higher expression of AR mRNA in atria compared to ventricles was observed in neonatal mouse. A positive correlation between mRNA levels of AR and Nppa was observed in mouse heart at early postnatal development. Androgen receptor expression is similar in males and females during cardiac development. Finally, androgen receptor protein was observed by immunohistochemistry in myocardial cells of atria and ventricles from 12.5 days onwards and restricted after 16.5 days post-coitum to nuclei of cardiomyocytes.</p><p><strong>Conclusion: </strong>Present results provide evidence that androgen receptor is expressed from prenatal stages in mouse heart, supporting the proposition that androgens could be involved in mammalian heart development.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-017-0033-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35411433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfide high mobility group box-1 causes bladder pain through bladder Toll-like receptor 4.","authors":"Fei Ma,&nbsp;Dimitrios E Kouzoukas,&nbsp;Katherine L Meyer-Siegler,&nbsp;Karin N Westlund,&nbsp;David E Hunt,&nbsp;Pedro L Vera","doi":"10.1186/s12899-017-0032-9","DOIUrl":"https://doi.org/10.1186/s12899-017-0032-9","url":null,"abstract":"<p><strong>Background: </strong>Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain. Therefore, we investigated whether intravesical administration of specific HMGB1 redox forms caused abdominal mechanical hypersensitivity, micturition changes, and bladder inflammation in female C57BL/6 mice 24 hours post-administration. Moreover, we determined which of the specific HMGB1 receptors, Toll-like receptor 4 (TLR4) or receptor for advanced glycation end products (RAGE), mediate HMGB1-induced changes.</p><p><strong>Results: </strong>Disulfide HMGB1 elicited abdominal mechanical hypersensitivity 24 hours after intravesical (5, 10, 20 μg/150 μl) instillation. In contrast, all-thiol HMGB1 did not produce abdominal mechanical hypersensitivity in any of the doses tested (1, 2, 5, 10, 20 μg/150 μl). Both HMGB1 redox forms caused micturition changes only at the highest dose tested (20 μg/150 μl) while eliciting mild bladder edema and reactive changes at all doses. We subsequently tested whether the effects of intravesical disulfide HMGB1 (10 μg/150 μl; a dose that did not produce inflammation) were prevented by systemic (i.p.) or local (intravesical) administration of either a TLR4 antagonist (TAK-242) or a RAGE antagonist (FPS-ZM1). Systemic administration of either TAK-242 (3 mg/kg) or FPS-ZM1 (10 mg/kg) prevented HMGB1 induced abdominal mechanical hypersensitivity while only intravesical TLR4 antagonist pretreatment (1.5 mg/ml; not RAGE) had this effect.</p><p><strong>Conclusions: </strong>The disulfide form of HMGB1 mediates bladder pain directly (not secondary to inflammation or injury) through activation of TLR4 receptors in the bladder. Thus, TLR4 receptors are a specific local target for bladder pain.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-017-0032-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35029109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial dysfunction in the pathogenesis of pre-eclampsia in Ghanaian women.","authors":"Kwame Adu-Bonsaffoh, Daniel Ansong Antwi, Ben Gyan, Samuel Amenyi Obed","doi":"10.1186/s12899-017-0029-4","DOIUrl":"10.1186/s12899-017-0029-4","url":null,"abstract":"<p><strong>Background: </strong>Pre-eclampsia (PE) remains a disease of theories despite extensive research into its etiology. Alteration in the production of vascular endothelial growth factor (VEGF), a biomarker of endothelial dysfunction, is associated with pre-eclampsia although conflicting reports have been reported. The aim of the study was to determine and compare maternal serum levels of VEGF among pre-eclamptics, normotensive non pregnant and pregnant women. This was a cross-sectional study involving 100 women with pre-eclampsia, 102 women with normotensive pregnancy and 75 normotensives who were not pregnant. The study was carried out at Korle Bu Teaching Hospital (KBTH) from April to June in 2011. Basic socio-demographic and obstetric data were obtained by means of structured questionnaire. Following venesection, about 5mls of blood was sampled from the participants for the various tests. Enzyme Linked Immunosorbent Assay was used to determine the maternal serum levels of free VEGF. Data analysis was performed using SPSS version 20.</p><p><strong>Results: </strong>Significant reduction in median serum levels of free VEGF was seen in both, normal pregnant [84.06 pg/ml (IQR: 78.90-99.67)] and pre-eclamptic women [4.71 pg/ml, (IQR: 3.41-7.93)] compared to the non-pregnant (395.85 pg/ml, IQR 234.93-625) with p < 0.001; the reduction was far greater in the pre-eclamptic group compared to that of normotensive pregnant group (p < 0.001). Early-onset pre-eclampsia had significantly more severe reduction in free VEGF levels (3.89, IQR: 2.60-5.67 pg/ml) compared to that of late onset PE (5.23, IQR: 3.78-16.97 pg/ml) with p<0.001 indicating a severer endothelial damage in former.</p><p><strong>Conclusions: </strong>Endothelial dysfunction contributes significantly to the pathogenesis of pre-eclampsia as demonstrated by profound decrease in maternal serum VEGF levels in PE compared to normotensive pregnancy and non-pregnancy state. The pathophysiology of early-onset pre-eclampsia may be partly explained by marked reduction in free serum VEGF levels with resultant severe endothelial dysfunction.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34867778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term overfeeding of zebrafish with normal or high-fat diet as a model for the development of metabolically healthy versus unhealthy obesity.","authors":"Kathrin Landgraf,&nbsp;Susanne Schuster,&nbsp;Andrej Meusel,&nbsp;Antje Garten,&nbsp;Thomas Riemer,&nbsp;Dorit Schleinitz,&nbsp;Wieland Kiess,&nbsp;Antje Körner","doi":"10.1186/s12899-017-0031-x","DOIUrl":"https://doi.org/10.1186/s12899-017-0031-x","url":null,"abstract":"<p><strong>Background: </strong>Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). However, the exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be specifically induced. In the current study, we aimed to establish a protocol for the use of zebrafish as a model for obesity-related metabolically healthy versus metabolically unhealthy AT accumulation.</p><p><strong>Methods: </strong>We overfed adult male zebrafish of the AB strain with normal fat diet (NFD) or high fat diet (HFD) for 8 weeks and compared parameters related to obesity, i.e. body weight, body mass index, condition index and body fat percentage, to control zebrafish fed under physiological conditions. In addition, we investigated the presence of early obesity-related metabolic alterations by quantifying blood glucose levels, plasma triglyceride and cholesterol levels, and by assessing ectopic lipid accumulation in the liver of zebrafish. Finally, we determined gene expression levels of marker genes related to lipid metabolism, inflammation and fibrosis in visceral AT and liver.</p><p><strong>Results: </strong>We show that 8-weeks overfeeding with either NFD or HFD leads to a significant increase in body weight and AT mass compared to controls. In contrast to NFD-overfed zebrafish, HFD-overfed zebrafish additionally present metabolic alterations, e.g. hyperglycemia and ectopic lipid accumulation in the liver, and a metabolically unhealthy AT phenotype with adipocyte hypertrophy especially in the visceral AT depot, which is accompanied by changes in the expression of marker genes for lipid metabolism, inflammation and fibrosis.</p><p><strong>Conclusions: </strong>In summary, we have established a method for the specific induction of metabolically distinct obesity phenotypes in zebrafish. Our results indicate that zebrafish represents an attractive model to study regulatory mechanisms involved in the determination of AT phenotype during development of metabolically healthy versus metabolically unhealthy obesity.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-017-0031-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34841058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age.","authors":"I Webster,&nbsp;R Salie,&nbsp;E Marais,&nbsp;W-J Fan,&nbsp;G Maarman,&nbsp;B Huisamen,&nbsp;A Lochner","doi":"10.1186/s12899-017-0030-y","DOIUrl":"https://doi.org/10.1186/s12899-017-0030-y","url":null,"abstract":"<p><strong>Background: </strong>Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential.</p><p><strong>Methods: </strong>Four groups of Wistar male rats were used: age-matched controls (AMC) receiving standard rat chow for (i) 16 weeks and (ii) 16 months respectively; DIO rats receiving a sucrose-supplemented diet for (iii) 16 weeks and (iv) 16 months respectively. The ages of groups (i) and (iii) were 22 weeks (\"young\") and groups (ii) and (iv) 17 months (\"middle-aged\") at time of experimentation. Isolated perfused working hearts were subjected to 35 min regional ischaemia/1 h reperfusion. Endpoints were infarct size (tetrazolium staining) and functional recovery. Hearts were preconditioned by 3 × 5 min ischaemia/5 min reperfusion. Results were processed using GraphPad Prism statistical software.</p><p><strong>Results: </strong>Age did not affect baseline heart function before induction of ischaemia and I/R damage as indicated by infarct size and similar values were obtained in hearts from both age groups. Age also had no effect on functional recovery of hearts during reperfusion after regional ischaemia in AMC rats, but cardiac output during reperfusion was better in hearts from middle-aged than young DIO rats. The diet reduced infarct size in hearts from young rats (% of area at risk: AMC: 32.4 ± 3.6; DIO: 20.7 ± 2.9, p < 0.05), with no differences in hearts from middle-aged rats (AMC: 24.6 ± 4.6; DIO: 28.3 ± 13.5, p = NS). Compared to their respective AMC, diet-induced obesity had no significant effect on functional recovery of hearts from both age groups after exposure to regional ischaemia. When exposed to the more severe stress of global ischaemia, the functional recovery potential of middle-aged DIO rats appeared to be impeded compared to hearts of young DIO rats, while age had no effect on the functional recovery of AMC hearts. Preconditioning reduced infarct size in hearts from young control rats and both middle-aged groups, but not from young DIO rats. Age had a significant effect on functional recovery in preconditioning: it was improved in hearts from young control and DIO rats, but depressed in both middle-aged groups.</p><p><strong>Conclusions: </strong>The data showed that middle-age and obesity had no effect on baseline myocardial function and did not increase susceptibility to I/R damage upon exposure to regional ischaemia. On the contrary, obesity reduced I/R damage in young rats. Preconditioned aging hearts showed a decreased infarct size, but a reduction in functional recovery.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-017-0030-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34818634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}