scholarly journals Metabolomic Profiles of Mouse Tissues Reveal an Interplay between Aging and Energy Metabolism

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 17
Author(s):  
Qishun Zhou ◽  
Jakob Kerbl-Knapp ◽  
Fangrong Zhang ◽  
Melanie Korbelius ◽  
Katharina Barbara Kuentzel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Metabolic Changes ◽  
Lipid Storage ◽  
Wild Type ◽  
Mixed Genetic Background ◽  
Mouse Tissues ◽  
Different Parts

Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of the aging process. However, the metabolic changes in tissues responsible for food intake and lipid storage have remained unexplored. In this study, we aimed to investigate aging-related metabolic alterations in these tissues. To fill this gap, we employed NMR-based metabolomics in several tissues, including different parts of the intestine (duodenum, jejunum, ileum) and brown/white adipose tissues (BAT, WAT), of young (9–10 weeks) and old (96–104 weeks) wild-type (mixed genetic background of 129/J and C57BL/6) mice. We, further, included plasma and skeletal muscle of the same mice to verify previous results. Strikingly, we found that duodenum, jejunum, ileum, and WAT do not metabolically age. In contrast, plasma, skeletal muscle, and BAT show a strong metabolic aging phenotype. Overall, we provide first insights into the metabolic changes of tissues essential for nutrient uptake and lipid storage and have identified biomarkers for metabolites that could be further explored, to study the molecular mechanisms of aging.

scholarly journals Metabolomic Profiles of Mice Tissues Reveals an Interplay Between Aging and Energy Metabolism

2021 ◽  
Author(s):  
Qishun Zhou ◽  
Jakob Kerbl-Knapp ◽  
Fangrong Zhang ◽  
Melanie Korbelius ◽  
Katharina Barbara Kuentzel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Molecular Basis ◽  
Genetic Background ◽  
Molecular Mechanisms ◽  
Metabolic Changes ◽  
Lipid Storage ◽  
Wild Type ◽  
Mixed Genetic Background ◽  
Different Parts

Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of aging process. However, the metabolic changes in tissues responsible for food intake and lipid storage have remained unexplored. In this study, we aimed to investigate aging-related metabolic alterations in these tissues. To fill this gap, we employed NMR-based metabolomics in several tissues, including different parts of the intestine (duodenum, jejunum, ileum) and brown/white adipose tissues (BAT, WAT) of young (9-10 weeks) and old (96-104 weeks) wild-type (mixed genetic background of 129/J and C57BL/6) mice. We further included plasma and skeletal muscle of the same mice to verify previous results. Strikingly, we found that duodenum, jejunum, ileum, and WAT do not metabolically age. In contrast, plasma, skeletal muscle, and BAT show a strong metabolic aging phenotype. Overall, we provide first insights into the metabolic changes of tissues essential for nutrient uptake and lipid storage and have identified biomarkers for metabolites that could be further explored to study the molecular mechanisms of aging.

TRPV4 deficiency increases skeletal muscle metabolic capacity and resistance against diet-induced obesity

2012 ◽  
Vol 112 (7) ◽  
pp. 1223-1232 ◽  
Author(s):  
Tatsuya Kusudo ◽  
Zhonghua Wang ◽  
Atsuko Mizuno ◽  
Makoto Suzuki ◽  
Hitoshi Yamashita
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Transient Receptor Potential ◽  
Thermal Sensation ◽  
Chow Diet ◽  
Type I ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Obesity In Mice

Transient receptor potential channel V4 (TRPV4) functions as a nonselective cation channel in various cells and plays physiological roles in osmotic and thermal sensation. However, the function of TRPV4 in energy metabolism is unknown. Here, we report that TRPV4 deficiency results in increased muscle oxidative capacity and resistance to diet-induced obesity in mice. Although no difference in body weight was observed between wild-type and Trpv4−/− mice when fed a standard chow diet, obesity phenotypes induced by a high-fat diet were significantly improved in Trpv4−/− mice, without any change in food intake. Quantitative analysis of mRNA revealed the constitutive upregulation of many genes, including those for transcription factors such as peroxisome proliferator-activated receptor α and for metabolic enzymes such as phosphoenolpyruvate carboxykinase. These upregulated genes were especially prominent in oxidative skeletal muscle, in which the activity of Ca2+-dependent phosphatase calcineurin was elevated, suggesting that other Ca2+ channels function in the skeletal muscle of Trpv4−/− mice. Indeed, gene expressions for TRPC3 and TRPC6 increased in the muscles of Trpv4−/− mice compared with those of wild-type mice. The number of oxidative type I fiber also increased in the mutant muscles following myogenin gene induction. These results strongly suggested that inactivation of Trpv4 induces compensatory increases in TRPC3 and TRPC6 production, and elevation of calcineurin activity, affecting energy metabolism through increased expression of genes involved in fuel oxidation in skeletal muscle and thereby contributing to increased energy expenditure and protection from diet-induced obesity in mice.

scholarly journals OR-035 Effect of Aerobic Training on the Exercise Capacity of Apelin Knock-out Mice

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lu Yan ◽  
Tieying Li ◽  
Ying Zhang
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Oxygen Uptake ◽  
Exercise Capacity ◽  
Aerobic Training ◽  
Movement Time ◽  
Wild Type ◽  
Running Speed ◽  
Knock Out ◽  
Knock Out Mice

Objective Aerobic training is considered to be an effective way to enhance the body’s exercise capacity which is closely related to the improvement of skeletal muscle energy metabolism. And as a new myokine, apelin has been found to play a key role in regulating the energy metabolism of skeletal muscle. However, whether the loss of apelin gene affects exercise capacity and what role aerobic training play in it remains unknown. This study was designed to investigate the effect of apelin on exercise capacity during aerobic training and to provide a theoretical basis for the mechanism of aerobic exercise affecting exercise capacity. Methods Male C57BL/6J wild type mouse(n=20) and apelin knock-out mouse(n=20) were assigned by random allocation to four groups(n=10): wild type control(WC), wild type exercised(WE), apelin knock-out control(KC) and apelin knock-out exercised(KE). Exercise training consisted of treadmill running 60 minutes/day ×6 days/week for 4 weeks. The training intensity corresponded to the 70-75% maximum oxygen uptake of mice. The running speed was 15m/min with an incline of +5° in the first 2 weeks and subsequently adjusted to 20m/min according to the maximum oxygen uptake in the last 2 weeks. On the day after training, all groups were forced to perform a incremental exercise test to exhaustion. This test was started with an incline of +5°and a speed of 10 m/min for 5 min. After this initial phase, the speed was progressively increased by 3m/min every 3 min until animal exhausted. The maximum running speed, movement time and distance were recorded during the test. Results Compared with group WC, the maximum running speed, movement time and distance of group KC were significantly decreased(P<0.01). And the maximum running speed, movement time and distance of group KE were clearly higher than those of group KC(P<0.01). There is no significant difference between group WE and group WC, and between group KE and group WE. Conclusions The exercise capacity of mice was significantly decreased because of knocking out the apelin gene, and the exercise ability of apelin knock-out mice can be clearly enhanced by aerobic training.

scholarly journals Molecular Basis of p53 Functional Inactivation by the Leukemic Protein MLL-ELL

2003 ◽  
Vol 23 (12) ◽  
pp. 4230-4246 ◽  
Author(s):  
Dmitri Wiederschain ◽  
Hidehiko Kawai ◽  
JiJie Gu ◽  
Ali Shilatifard ◽  
Zhi-Min Yuan
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Wild Type ◽  
Efficient Inhibitor ◽  
C Terminus ◽  
Functional Inactivation ◽  
Necessary And Sufficient ◽  
First Time

ABSTRACT The Eleven Lysine-rich Leukemia (ELL) gene undergoes translocation and fuses in frame to the Multiple Lineage Leukemia (MLL) gene in a substantial proportion of patients suffering from acute forms of leukemia. Molecular mechanisms of cellular transformation by the MLL-ELL fusion are not well understood. Although both MLL-ELL and wild-type ELL can reduce functional activity of p53 tumor suppressor, our data reveal that MLL-ELL is a much more efficient inhibitor of p53 than is wild-type ELL. We also demonstrate for the first time that ELL extreme C terminus [ELL(eCT)] is required for the recruitment of p53 into MLL-ELL nuclear foci and is both necessary and sufficient for the MLL-ELL inhibition of p53-mediated induction of p21 and apoptosis. Finally, our results demonstrate that MLL-ELL requires the presence of intact ELL(eCT) in order to disrupt p53 interactions with p300/CBP coactivator and thus significantly reduce p53 acetylation in vivo. Since ELL(eCT) has recently been shown to be both necessary and sufficient for MLL-ELL-mediated transformation of normal blood progenitors, our data correlate ELL(eCT) contribution to MLL-ELL transformative effects with its ability to functionally inhibit p53.

scholarly journals Tissue-Specific Landscape of Metabolic Dysregulation During Ageing

2020 ◽  
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Alena Akhmetshina ◽  
Melanie Korbelius ◽  
Katharina Küntzel ◽  
...  
Keyword(s):  
Metabolic Changes ◽  
Wild Type ◽  
Specific Level ◽  
Tissue Specific ◽  
Drug Candidates ◽  
Mixed Genetic Background ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Kidney Liver ◽  
Target Effects

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted a metabolomic analysis of brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild type (mixed genetic background of 129/J and C57BL/6) mice using NMR spectroscopy. We found differences in metabolic fingerprints of all tissues and identified several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to age determine the age of biologic tissues and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

Mechanisms of ageing metabolic decline revealed by targeted metabolomics and energy metabolism in NAD+ depleted skeletal muscle

2016 ◽  
Author(s):  
Rachel Fletcher ◽  
Lucy Oldacre-Bartley ◽  
Craig Doig ◽  
Charles Brenner ◽  
Gareth Lavery
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Targeted Metabolomics

Epigenetic and Metabolic Changes in Skeletal Muscle Underlying the Improvement of Insulin Sensitivity after Bariatric Surgery in Humans

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 156-OR
Author(s):  
SOFIYA GANCHEVA ◽  
MERIEM OUNI ◽  
CHRYSI KOLIAKI ◽  
TOMAS JELENIK ◽  
DANIEL F. MARKGRAF ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Metabolic Changes

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Genetic mapping and transcriptomic characterization of a new fuzzless-tufted cottonseed mutant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian-Hao Zhu ◽  
Warwick Stiller ◽  
Philippe Moncuquet ◽  
Stuart Gordon ◽  
Yuman Yuan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Gene Families ◽  
Mutant Phenotype ◽  
Wild Type ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Flanking Region ◽  
Comparative Transcriptomic Analysis

Abstract Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.

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