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  1. Article ; Online: NRF2 function in osteocytes is required for bone homeostasis and drives osteocytic gene expression

    Cristina Sánchez-de-Diego / Leonardo Pedrazza / Carolina Pimenta-Lopes / Arturo Martinez-Martinez / Norma Dahdah / José Antonio Valer / Pablo Garcia-Roves / Jose Luis Rosa / Francesc Ventura

    Redox Biology, Vol 40, Iss , Pp 101845- (2021)

    2021  

    Abstract: Osteocytes, the most abundant bone cell type, are derived from osteoblasts through a process in which they are embedded in an osteoid. We previously showed that nutrient restriction promotes the osteocyte transcriptional program and is associated with ... ...

    Abstract Osteocytes, the most abundant bone cell type, are derived from osteoblasts through a process in which they are embedded in an osteoid. We previously showed that nutrient restriction promotes the osteocyte transcriptional program and is associated with increased mitochondrial biogenesis. Here, we show that increased mitochondrial biogenesis increase reactive oxygen species (ROS) levels and consequently, NRF2 activity during osteocytogenesis. NRF2 activity promotes osteocyte-specific expression of Dmp1, Mepe, and Sost in IDG-SW3 cells, primary osteocytes, and osteoblasts, and in murine models with Nfe2l2 deficiency in osteocytes or osteoblasts. Moreover, ablation of Nfe2l2 in osteocytes or osteoblasts generates osteopenia and increases osteoclast numbers with marked sexual dimorphism. Finally, treatment with dimethyl fumarate prevented the deleterious effects of ovariectomy in trabecular bone masses of mice and restored osteocytic gene expression. Altogether, we uncovered the role of NRF2 activity in osteocytes during the regulation of osteocyte gene expression and maintenance of bone homeostasis.
    Keywords Bone ; Osteocyte ; NRF2 ; Oxidative stress ; Osteoporosis ; Bone homeostasis ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate

    Isabel Huber-Ruano / Enrique Calvo / Jordi Mayneris-Perxachs / M-Mar Rodríguez-Peña / Victòria Ceperuelo-Mallafré / Lídia Cedó / Catalina Núñez-Roa / Joan Miro-Blanch / María Arnoriaga-Rodríguez / Aurélie Balvay / Claire Maudet / Pablo García-Roves / Oscar Yanes / Sylvie Rabot / Ghjuvan Micaelu Grimaud / Annachiara De Prisco / Angela Amoruso / José Manuel Fernández-Real / Joan Vendrell /
    Sonia Fernández-Veledo

    Microbiome, Vol 10, Iss 1, Pp 1-

    2022  Volume 22

    Abstract: Abstract Background Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is ... ...

    Abstract Abstract Background Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting. Results Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp. Conclusions Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation. Video Abstract
    Keywords Succinate ; Obesity ; Probiotics ; Animal models ; Inflammation ; Glucose tolerance ; Microbial ecology ; QR100-130
    Subject code 616
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease

    Sandra Torres / Nuria Matías / Anna Baulies / Susana Nuñez / Cristina Alarcon-Vila / Laura Martinez / Natalia Nuño / Anna Fernandez / Joan Caballeria / Thierry Levade / Alba Gonzalez-Franquesa / Pablo Garcia-Rovés / Elisa Balboa / Silvana Zanlungo / Gemma Fabrías / Josefina Casas / Carlos Enrich / Carmen Garcia-Ruiz / José C. Fernández-Checa

    Redox Biology, Vol 11, Iss , Pp 60-

    2017  Volume 72

    Abstract: Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature ... ...

    Abstract Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH) depletion, we investigated the impact of mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE), but not N-acetylcysteine (NAC), restored the mGSH pool in liver and brain of Npc1-/- mice and in fibroblasts from NPC patients, while both GSH-EE and NAC increased total GSH levels. GSH-EE but not NAC increased the median survival and maximal life span of Npc1-/- mice. Moreover, intraperitoneal therapy with GSH-EE protected against oxidative stress and oxidant-induced cell death, restored calbindin levels in cerebellar Purkinje cells and reversed locomotor impairment in Npc1-/- mice. High-resolution respirometry analyses revealed that GSH-EE improved oxidative phosphorylation, coupled respiration and maximal electron transfer in cerebellum of Npc1-/- mice. Lipidomic analyses showed that GSH-EE treatment had not effect in the profile of most sphingolipids in liver and brain, except for some particular species in brain of Npc1-/- mice. These findings indicate that the specific replenishment of mGSH may be a potential promising therapy for NPC disease, worth exploring alone or in combination with other options. Keywords: Ceramide, Sphingolipids, Mitochondrial GSH, Cerebellum, Hepatosplenomegaly, Lysosomal disorders
    Keywords Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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