المؤلفون: Ester Díez-Sainz, Silvia Lorente-Cebrián, Paula Aranaz, Ez-Zoubir Amri, José I. Riezu-Boj, Fermín I. Milagro

المصدر: Frontiers in Nutrition, Vol 10 (2023)

مصطلحات موضوعية: CLEC7A, NFAM1, TLR6, microRNA, cross-kingdom regulation, diet, Nutrition. Foods and food supply, TX341-641

الوصف: BackgroundEdible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.MethodsMicroRNAs from plant-derived foods were identified by next-generation sequencing. MicroRNAs with inflammatory putative targets were selected, after performing in silico analyses. The expression of candidate plant-derived miRNAs was analyzed by qPCR in edible plant-derived foods and their effects were evaluated in THP-1 monocytes differentiated to macrophages. The bioavailability of candidate plant miRNAs in humans was evaluated in feces and serum samples by qPCR.ResultsmiR482f and miR482c-5p are present in several edible plant-derived foods, such as fruits, vegetables, and cooked legumes and cereals, and fats and oils. Transfections with miR482f and miR482c-5p mimics decreased the gene expression of CLEC7A and NFAM1, and TRL6, respectively, in human THP-1 monocytes differentiated to macrophages, which had an impact on gene expression profile of inflammatory biomarkers. Both microRNAs (miR482f and miR482c-5p) resisted degradation during digestion and were detected in human feces, although not in serum.ConclusionOur findings suggest that miR482f and miR482c-5p can promote an anti-inflammatory gene expression profile in human macrophages in vitro and their bioavailability in humans can be achieved through diet, but eventually restricted at the gut level.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnut.2023.1287312/fullTest; https://doaj.org/toc/2296-861XTest

الوصول الحر: https://doaj.org/article/f42e5851ebda4b8ea2104719a7aa270aTest

المؤلفون: Mueez U-Din, Vanessa D. de Mello, Marjo Tuomainen, Juho Raiko, Tarja Niemi, Tobias Fromme, Anton Klåvus, Nadine Gautier, Kimmo Haimilahti, Marko Lehtonen, Karsten Kristiansen, John W. Newman, Kirsi H. Pietiläinen, Jussi Pihlajamäki, Ez-Zoubir Amri, Martin Klingenspor, Pirjo Nuutila, Eija Pirinen, Kati Hanhineva, Kirsi A. Virtanen

المصدر: Cell Reports, Vol 42, Iss 9, Pp 113131- (2023)

مصطلحات موضوعية: CP: Metabolism, Biology (General), QH301-705.5

الوصف: Summary: Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211124723011439Test; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/1c0fa9c527de49b8bd7b766598b67913Test

المؤلفون: Ester Díez-Sainz, Paula Aranaz, Ez-Zoubir Amri, José I. Riezu-Boj, Silvia Lorente-Cebrián, Fermín I. Milagro

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 3, p 1721 (2024)

مصطلحات موضوعية: plant microRNA, cross-kingdom regulation, metabolism, fatty liver, NAFLD, steatosis, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations are needed to determine the potential impact of plant miRNAs in NAFLD. This study aimed to identify plant miRNAs that could eventually modulate the expression of human metabolic genes and protect against the progression of hepatic steatosis. Plant miRNAs from the miRBase were used to predict human target genes, and miR8126-3p and miR8126-5p were selected as candidates for their potential role in inhibiting glucose and lipid metabolism-related genes. Human HepG2 cells were transfected with plant miRNA mimics and then exposed to a mixture of oleic and palmitic acids to mimic steatosis. miR8126-3p and miR8126-5p transfections inhibited the expression of the putative target genes QKI and MAPKAPK2, respectively, and had an impact on the expression profile of key metabolic genes, including PPARA and SREBF1. Quantification of intrahepatic triglycerides revealed that miR8126-3p and miR8126-5p attenuated lipid accumulation. These findings suggest that plant miR8126-3p and miR8126-5p would induce metabolic changes in human hepatocytes eventually protecting against lipid accumulation, and thus, they could be potential therapeutic tools for preventing and alleviating lipid accumulation.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/3/1721Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/320c980abc3c4c8db5c801e056bfebffTest

المؤلفون: Lucia Balazova, Miroslav Balaz, Carla Horvath, Áron Horváth, Caroline Moser, Zuzana Kovanicova, Adhideb Ghosh, Umesh Ghoshdastider, Vissarion Efthymiou, Elke Kiehlmann, Wenfei Sun, Hua Dong, Lianggong Ding, Ez-Zoubir Amri, Pirjo Nuutila, Kirsi A. Virtanen, Tarja Niemi, Barbara Ukropcova, Jozef Ukropec, Pawel Pelczar, Thorsten Lamla, Bradford Hamilton, Heike Neubauer, Christian Wolfrum

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)

مصطلحات موضوعية: Science

الوصف: Activation of thermogenic adipocytes is a strategy to combat metabolic diseases. Here the authors report that GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1, and contributes to the regulation of glucose and energy metabolism.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/88ee4530cad64964a1bb8fbac9b2b659Test

المؤلفون: Muhammad Hamza Bokhari, Carina Halleskog, Alice Åslund, Nathalie Boulet, Eva Casadesús Rendos, Jasper Martin Anton de Jong, Robert Csikasz, Ez-Zoubir Amri, Irina Shabalina, Tore Bengtsson

المصدر: Communications Biology, Vol 4, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Bokhari et al. demonstrate mature murine brown and brite adipocytes produce quantifiable heat with β3-AR stimulation. They indicate that the essential component of this mechanism is UCP1 by using adipocytes lacking the protein.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2399-3642Test

الوصول الحر: https://doaj.org/article/c08d8b76080e4cb29b259c68ed19fbe9Test

المؤلفون: Cécilia Colson, Pierre-Louis Batrow, Sebastian Dieckmann, Laura Contu, Christian H. Roux, Laurence Balas, Claire Vigor, Baptiste Fourmaux, Nadine Gautier, Nathalie Rochet, Nathalie Bernoud-Hubac, Thierry Durand, Dominique Langin, Martin Klingenspor, Ez-Zoubir Amri

المصدر: Cells, Vol 12, Iss 3, p 446 (2023)

مصطلحات موضوعية: brown adipocyte, white adipocyte, conversion, PGI2, TXA2, FAHFA, Cytology, QH573-671

الوصف: Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4409/12/3/446Test; https://doaj.org/toc/2073-4409Test

الوصول الحر: https://doaj.org/article/7f11fa2e039647608c31a2d3a57a52e1Test

المؤلفون: Georges Raad, Fabrizio Serra, Luc Martin, Marie-Alix Derieppe, Jérôme Gilleron, Vera L Costa, Didier F Pisani, Ez-Zoubir Amri, Michele Trabucchi, Valerie Grandjean

المصدر: eLife, Vol 10 (2021)

مصطلحات موضوعية: epigenetic, inheritance, sperm, obesity, Medicine, Science, Biology (General), QH301-705.5

الوصف: Obesity is a growing societal scourge. Recent studies have uncovered that paternal excessive weight induced by an unbalanced diet affects the metabolic health of offspring. These reports mainly employed single-generation male exposure. However, the consequences of multigenerational unbalanced diet feeding on the metabolic health of progeny remain largely unknown. Here, we show that maintaining paternal Western diet feeding for five consecutive generations in mice induces an enhancement in fat mass and related metabolic diseases over generations. Strikingly, chow-diet-fed progenies from these multigenerational Western-diet-fed males develop a ‘healthy’ overweight phenotype characterized by normal glucose metabolism and without fatty liver that persists for four subsequent generations. Mechanistically, sperm RNA microinjection experiments into zygotes suggest that sperm RNAs are sufficient for establishment but not for long-term maintenance of epigenetic inheritance of metabolic pathologies. Progressive and permanent metabolic deregulation induced by successive paternal Western-diet-fed generations may contribute to the worldwide epidemic of metabolic diseases.

وصف الملف: electronic resource

العلاقة: https://elifesciences.org/articles/61736Test; https://doaj.org/toc/2050-084XTest

الوصول الحر: https://doaj.org/article/a53a94fde4e94facb24dc53adb55cc91Test

المؤلفون: Antoine Leboucher, Didier F. Pisani, Laura Martinez-Gili, Julien Chilloux, Patricia Bermudez-Martin, Anke Van Dijck, Tariq Ganief, Boris Macek, Jérôme A.J. Becker, Julie Le Merrer, R. Frank Kooy, Ez-Zoubir Amri, Edouard W. Khandjian, Marc-Emmanuel Dumas, Laetitia Davidovic

المصدر: Molecular Metabolism, Vol 21, Iss , Pp 22-35 (2019)

مصطلحات موضوعية: Internal medicine, RC31-1245

الوصف: Objectives: The Fragile X Mental Retardation Protein (FMRP) is a widely expressed RNA-binding protein involved in translation regulation. Since the absence of FMRP leads to Fragile X Syndrome (FXS) and autism, FMRP has been extensively studied in brain. The functions of FMRP in peripheral organs and on metabolic homeostasis remain elusive; therefore, we sought to investigate the systemic consequences of its absence. Methods: Using metabolomics, in vivo metabolic phenotyping of the Fmr1-KO FXS mouse model and in vitro approaches, we show that the absence of FMRP induced a metabolic shift towards enhanced glucose tolerance and insulin sensitivity, reduced adiposity, and increased β-adrenergic-driven lipolysis and lipid utilization. Results: Combining proteomics and cellular assays, we highlight that FMRP loss increased hepatic protein synthesis and impacted pathways notably linked to lipid metabolism. Mapping metabolomic and proteomic phenotypes onto a signaling and metabolic network, we predicted that the coordinated metabolic response to FMRP loss was mediated by dysregulation in the abundances of specific hepatic proteins. We experimentally validated these predictions, demonstrating that the translational regulator FMRP associates with a subset of mRNAs involved in lipid metabolism. Finally, we highlight that FXS patients mirror metabolic variations observed in Fmr1-KO mice with reduced circulating glucose and insulin and increased free fatty acids. Conclusions: Loss of FMRP results in a widespread coordinated systemic response that notably involves upregulation of protein translation in the liver, increased utilization of lipids, and significant changes in metabolic homeostasis. Our study unravels metabolic phenotypes in FXS and further supports the importance of translational regulation in the homeostatic control of systemic metabolism. Keywords: Fragile X mental retardation protein, RNA-binding protein, Translation, Metabolism, Glucose, Lipids

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2212877818311591Test; https://doaj.org/toc/2212-8778Test

الوصول الحر: https://doaj.org/article/bf35ddf6316a40d5be9efe3bf42b1cc8Test

المؤلفون: Serena Barilla, Ning Liang, Enrichetta Mileti, Raphaëlle Ballaire, Marie Lhomme, Maharajah Ponnaiah, Sophie Lemoine, Antoine Soprani, Jean-Francois Gautier, Ez-Zoubir Amri, Wilfried Le Goff, Nicolas Venteclef, Eckardt Treuter

المصدر: Molecular Metabolism, Vol 42, Iss , Pp 101066- (2020)

مصطلحات موضوعية: Adipocytes, Adipogenesis, Hypertrophy, Obesity, Type 2 diabetes, GPS2, Internal medicine, RC31-1245

الوصف: Objective: Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes. Methods: We generated a unique loss-of-function model by RNAi depletion of GPS2 in human multipotent adipose-derived stem (hMADS) cells. We thoroughly characterized the coregulator depletion-dependent pathway alterations during adipocyte differentiation at the level of transcriptome (RNA-seq), epigenome (ChIP-seq H3K27ac), cistrome (ChIP-seq GPS2), and lipidome. We validated the in vivo relevance of the identified pathways in non-diabetic and diabetic obese patients. Results: The loss of GPS2 triggers the reprogramming of cellular processes related to adipocyte differentiation by increasing the responses to the adipogenic cocktail. In particular, GPS2 depletion increases the expression of BMP4, an important trigger for the commitment of fibroblast-like progenitors toward the adipogenic lineage and increases the expression of inflammatory and metabolic genes. GPS2-depleted human adipocytes are characterized by hypertrophy, triglyceride and phospholipid accumulation, and sphingomyelin depletion. These changes are likely a consequence of the increased expression of ATP-binding cassette subfamily G member 1 (ABCG1) that mediates sphingomyelin efflux from adipocytes and modulates lipoprotein lipase (LPL) activity. We identify ABCG1 as a direct transcriptional target, as GPS2 depletion leads to coordinated changes of transcription and H3K27 acetylation at promoters and enhancers that are occupied by GPS2 in wild-type adipocytes. We find that in omental adipose tissue of obese humans, GPS2 levels correlate with ABCG1 levels, type 2 diabetic status, and lipid metabolic status, supporting the in vivo relevance of the hMADS cell-derived in vitro data. Conclusion: Our study reveals a dual regulatory role of GPS2 in epigenetically modulating the chromatin landscape and gene expression during human adipocyte differentiation and identifies a hitherto unknown GPS2-ABCG1 pathway potentially linked to adipocyte hypertrophy in humans.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S221287782030140XTest; https://doaj.org/toc/2212-8778Test

الوصول الحر: https://doaj.org/article/f460bff5fd63430e99e9c9d70a40b52dTest

المؤلفون: Hang Wu, Taner Pula, Daniel Tews, Ez-Zoubir Amri, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky, Julian Roos

المصدر: Cells, Vol 10, Iss 11, p 3205 (2021)

مصطلحات موضوعية: microRNA-27a, adipocytes, adipogenesis, PPARγ, LPL, Cytology, QH573-671

الوصف: MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology. Both strands of miR-27a, miR-27a-3p and -5p, were downregulated during the adipogenic differentiation of Simpson–Golabi–Behmel syndrome (SGBS) cells, human multipotent adipose-derived stem cells (hMADS), and human primary adipose-derived stromal cells (hASCs). Using miRNA-mimic transfection, we observed that miR-27a-3p is a crucial regulator of adipogenesis, while miR-27a-5p did not alter the differentiation capacity in SGBS cells. In silico screening predicted lipoprotein lipase (LPL) and peroxisome proliferator activated receptor γ (PPARγ) as potential targets of miR-27a-3p. The downregulation of both genes was verified in vitro, and the interaction of miR-27-3p with target sites in the 3′ UTRs of both genes was confirmed via a miRNA-reporter-gene assay. Here, the knockdown of LPL did not interfere with adipogenic differentiation, while PPARγ knockdown decreased adipogenesis significantly, suggesting that miR-27-3p exerts its inhibitory effect on adipogenesis by repressing PPARγ. Taken together, we identified and validated a crucial role for miR-27a-3p in human adipogenesis played by targeting the essential adipogenic transcription factor PPARγ. Though we confirmed LPL as an additional target of miR-27a-3p, it does not appear to be involved in regulating human adipogenesis. Thereby, our findings call the conclusions drawn from previous studies, which identified LPL as a crucial regulator for murine and human adipogenesis, into question.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4409/10/11/3205Test; https://doaj.org/toc/2073-4409Test

الوصول الحر: https://doaj.org/article/64fd73d8552c41d4896d5fdb68c64986Test