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  1. Article ; Online: Physical exercise elicits UPR

    Gaspar, Rodrigo Stellzer / Katashima, Carlos Kiyoshi / Crisol, Barbara Moreira / Carneiro, Fernanda Silva / Sampaio, Igor / Silveira, Leonardo Dos Reis / Silva, Adelino Sanchez Ramos da / Cintra, Dennys Esper / Pauli, José Rodrigo / Ropelle, Eduardo Rochete

    Molecular metabolism

    2023  Volume 78, Page(s) 101816

    Abstract: Objective: The mitochondrial unfolded protein response (UPR: Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.: Results: Firstly, RNA sequencing ... ...

    Abstract Objective: The mitochondrial unfolded protein response (UPR
    Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.
    Results: Firstly, RNA sequencing and Western blotting analysis revealed that an acute aerobic session stimulated several mitostress-related genes and protein content in muscle, including the UPR
    Conclusion: Our findings provide new insights into how exercise triggers mitostress signals toward the oxidative capacity in the skeletal muscle.
    MeSH term(s) Animals ; Mice ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mitochondria/metabolism ; Muscle, Skeletal/metabolism ; Physical Conditioning, Animal ; Unfolded Protein Response ; Mitogen-Activated Protein Kinase 8/metabolism
    Chemical Substances JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 8 (EC 2.7.11.24)
    Language English
    Publishing date 2023-10-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2023.101816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4

    Muñoz, Vitor Rosetto / Botezelli, José Diego / Gaspar, Rafael Calais / da Rocha, Alisson L / Vieira, Renan Fudoli Lins / Crisol, Barbara Moreira / Braga, Renata Rosseto / Severino, Matheus Brandemarte / Nakandakari, Susana Castelo Branco Ramos / Antunes, Gabriel Calheiros / Brunetto, Sérgio Q / Ramos, Celso D / Velloso, Lício Augusto / Simabuco, Fernando Moreira / de Moura, Leandro Pereira / da Silva, Adelino Sanchez Ramos / Ropelle, Eduardo Rochete / Cintra, Dennys Esper / Pauli, José Rodrigo

    Cellular and molecular life sciences : CMLS

    2023  Volume 80, Issue 5, Page(s) 122

    Abstract: Objective: Intriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole- ... ...

    Abstract Objective: Intriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole-body glucose homeostasis. Therefore, we investigated the impact of short-term physical activity in a mouse model (Slc2a4
    Methods: Slc2a4
    Results: When Slc2a4
    Conclusions: Both short-term exercise protocols were efficient in whole-body glucose homeostasis and insulin resistance. While endurance exercise plays an important role in transcriptome and mitochondrial activity, strength exercise mostly affects post-translational mechanisms and protein synthesis in skeletal muscle. Thus, the performance of both types of physical exercise proved to be a very effective way to mitigate the impacts of hyperglycemia and hyperinsulinemia in the Slc2a4
    MeSH term(s) Mice ; Animals ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Muscle, Skeletal/metabolism ; Hyperglycemia/genetics ; Hyperglycemia/metabolism ; Glucose/metabolism ; Glucose Transporter Type 4/metabolism
    Chemical Substances Glucose (IY9XDZ35W2) ; Slc2a4 protein, mouse ; Glucose Transporter Type 4
    Language English
    Publishing date 2023-04-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-04771-2
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
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  3. Article ; Online: Aging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats.

    Gaspar, Rafael Calais / Muñoz, Vitor Rosetto / Nakandakari, Susana Castelo Branco Ramos / Vieira, Renan Fudoli Lins / da Conceição, Luciana Renata / de Oliveira, Fellipe / Crisol, Barbara Moreira / da Silva, Adelino S R / Cintra, Dennys Esper / de Moura, Leandro Pereira / Ropelle, Eduardo Rochete / Zaghloul, Iman / Mekary, Rania A / Pauli, José Rodrigo

    Experimental gerontology

    2020  Volume 139, Page(s) 111021

    Abstract: TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in multiple tissues and it has been implicated in stress response regulation and metabolic control. However, the role of hepatic TRB3 and its relationship with endoplasmic ... ...

    Abstract TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in multiple tissues and it has been implicated in stress response regulation and metabolic control. However, the role of hepatic TRB3 and its relationship with endoplasmic reticulum stress (ER stress) during aging has not been elucidated. Thus, the present study aimed to explore the association of aging with TRB3 and ER stress on the hepatic glucose production in Wistar rats. We found the TRB3 protein content to be higher in livers of old rats (27 months) compared to young (3 months) and middle-aged (17 months) rats. The increased content of hepatic TRB3 of the old rats was associated with insulin resistance (decreased protein kinase B (Akt) and Forkhead Box O1 (FoxO1) phosphorylation) and increased enzymes of gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase)). Moreover, aging was associated with activation of the endoplasmic reticulum stress pathway-related molecules, with an increase in phosphorylation of Inositol-requiring enzyme 1 (p-IRE1α), the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), eukaryotic translation initiation factor-α (p-eIF2α), binding immunoglobulin protein (BiP), and the C/EBP homologous protein (CHOP) contents in rats. These molecular changes resulted in increased liver glucose production in response to the pyruvate challenge and hyperglycemia of the old rats. In conclusion, our results suggested that, by interfering with insulin signaling in the liver, TRB3 was associated with ER stress and increased hepatic glucose production in aging rats.
    MeSH term(s) Aging ; Animals ; Endoplasmic Reticulum Stress ; Endoribonucleases ; Glucose ; Liver ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Rats ; Rats, Wistar
    Chemical Substances Trib3 protein, rat ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Endoribonucleases (EC 3.1.-) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2020-07-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2020.111021
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 579: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice.

    Gaspar, Rafael Calais / Muñoz, Vitor Rosetto / Kuga, Gabriel Keine / Nakandakari, Susana Castelo Branco Ramos / Crisol, Barbara Moreira / Lenhare, Luciene / Breda, Leonardo / Botezelli, José Diego / Sant'Ana, Marcella Ramos / da Silva, Adelino S R / Cintra, Dennys Esper / de Moura, Leandro Pereira / Ropelle, Eduardo Rochete / Pauli, José Rodrigo

    The European journal of neuroscience

    2019  Volume 50, Issue 7, Page(s) 3181–3190

    Abstract: Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. ... ...

    Abstract Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co-localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Eating/physiology ; Hypothalamus/metabolism ; Male ; Mice ; Phosphatidylinositol 3-Kinase/metabolism ; Physical Conditioning, Animal/physiology ; RNA, Messenger/metabolism ; Signal Transduction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Appl1 protein, mouse ; RNA, Messenger ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137)
    Language English
    Publishing date 2019-07-08
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.14490
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2548: Show issues Location:
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  5. Article ; Online: High-intensity exercise training induces mitonuclear imbalance and activates the mitochondrial unfolded protein response in the skeletal muscle of aged mice.

    Cordeiro, André Victor / Peruca, Guilherme Francisco / Braga, Renata Rosseto / Brícola, Rafael Santos / Lenhare, Luciene / Silva, Vagner Ramon Rodrigues / Anaruma, Chadi Pellegrini / Katashima, Carlos Kiyoshi / Crisol, Barbara Moreira / Barbosa, Lucas Torres / Simabuco, Fernando Moreira / da Silva, Adelino Sanchez Ramos / Cintra, Dennys Esper / de Moura, Leandro Pereira / Pauli, José Rodrigo / Ropelle, Eduardo Rochete

    GeroScience

    2020  Volume 43, Issue 3, Page(s) 1513–1518

    Abstract: The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis ... ...

    Abstract The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis and function. Here, we combined bioinformatics, physiological, and molecular analyses to examine the role of mitonuclear imbalance and UPRmt in the skeletal muscle of aged rodents and humans. The analysis of transcripts from the skeletal muscle of aged humans (60-70 years old) revealed that individuals with higher levels of UPRmt-related genes displayed a consistent increase in several mitochondrial-related genes, including the OXPHOS-associated genes. Interestingly, high-intensity interval training (HIIT) was effective in stimulating the mitonuclear imbalance and UPRmt in the skeletal muscle of aged mice. Furthermore, these results were accompanied by higher levels of several mitochondrial markers and improvements in physiological parameters and physical performance. These data indicate that the maintenance or stimulation of the mitonuclear imbalance and UPRmt in the skeletal muscle could ensure mitochondrial proteostasis during aging, revealing new insights into targeting mitochondrial metabolism by using physical exercise.
    MeSH term(s) Aging ; Animals ; High-Intensity Interval Training ; Mice ; Mitochondria/metabolism ; Muscle, Skeletal/metabolism ; Unfolded Protein Response
    Language English
    Publishing date 2020-07-31
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-020-00246-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  6. Article ; Online: Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice.

    Muñoz, Vitor Rosetto / Gaspar, Rafael Calais / Crisol, Barbara Moreira / Formigari, Guilherme Pedron / Sant'Ana, Marcella Ramos / Botezelli, José Diego / Gaspar, Rodrigo Stellzer / da Silva, Adelino S R / Cintra, Dennys Esper / de Moura, Leandro Pereira / Ropelle, Eduardo Rochete / Pauli, José Rodrigo

    The journal of physiological sciences : JPS

    2017  Volume 68, Issue 4, Page(s) 493–501

    Abstract: The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard ... ...

    Abstract The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard rodent chow; diet-induced obesity (DIO), fed an obesity-inducing diet; and a third group, which also received an obesity-inducing diet, but was subjected to an exercise training protocol (DIO + EXE). Protocol training was carried out for 1 h/d, 5 d/wk, for 8 weeks, performed at an intensity of 60% of exhaustion velocity. An insulin tolerance test (ITT) was performed in the last experimental week. Twenty-four hours after the last physical exercise session, the animals were euthanized and the liver was harvested for molecular analysis. Firstly, DIO mice showed increased epididymal fat and serum glucose and these results were accompanied by increased PCB and decreased p-Akt in hepatic tissue. On the other hand, physical exercise was able to increase the performance of the mice and attenuate PCB levels and hyperglycemia in DIO + EXE mice. The above findings show that physical exercise seems to be able to regulate hyperglycemia in obese mice, suggesting the participation of PCB, which was enhanced in the obese condition and attenuated after a treadmill running protocol. This is the first study to be aimed at the role of exercise training in hepatic PCB levels, which may be a novel mechanism that can collaborate to reduce the development of hyperglycemia and type 2 diabetes in DIO mice.
    MeSH term(s) Animals ; Blood Glucose/metabolism ; Hyperglycemia/metabolism ; Hyperglycemia/therapy ; Liver/metabolism ; Male ; Mice ; Mice, Obese ; Obesity/metabolism ; Phosphorylation ; Physical Conditioning, Animal/physiology ; Proto-Oncogene Proteins c-akt/metabolism ; Pyruvate Carboxylase/metabolism
    Chemical Substances Blood Glucose ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Pyruvate Carboxylase (EC 6.4.1.1)
    Language English
    Publishing date 2017-07-14
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2234472-X
    ISSN 1880-6562 ; 1880-6546
    ISSN (online) 1880-6562
    ISSN 1880-6546
    DOI 10.1007/s12576-017-0559-3
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    Uc I Zs.360: Show issues Location:
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  7. Article ; Online: Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.

    Katashima, Carlos Kiyoshi / de Oliveira Micheletti, Thayana / Braga, Renata Rosseto / Gaspar, Rodrigo Stellzer / Goeminne, Ludger J E / Moura-Assis, Alexandre / Crisol, Barbara Moreira / Brícola, Rafael S / Silva, Vagner Ramon R / de Oliveira Ramos, Camila / da Rocha, Alisson L / Tavares, Mariana Rosolen / Simabuco, Fernando Moreira / Matheus, Valquiria Aparecida / Buscaratti, Lucas / Marques-Souza, Henrique / Pazos, Patricia / Gonzalez-Touceda, David / Tovar, Sulay /
    Del Carmen García, María / Neto, Jose Cesar Rosa / Curi, Rui / Hirabara, Sandro Massao / Brum, Patrícia Chakur / Prada, Patrícia Oliveira / de Moura, Leandro P / Pauli, José Rodrigo / da Silva, Adelino S R / Cintra, Dennys Esper / Velloso, Licio A / Ropelle, Eduardo Rochete

    Science advances

    2022  Volume 8, Issue 30, Page(s) eabm7355

    Abstract: Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. ... ...

    Abstract Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation- and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.
    MeSH term(s) AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Animals ; Fatty Acids/metabolism ; Humans ; Hypothalamus/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Mice ; Muscle, Skeletal/metabolism ; Oxidation-Reduction
    Chemical Substances Fatty Acids ; Interleukin-6 ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2022-07-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abm7355
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