Équipe Mohammed Taouis

Neuroendocrinologie moléculaire de la prise alimentaire

En bref

NMPA étudie les mécanismes impliqués dans l’installation de la leptino- et insulino-résistances au niveau hypothalamique. Notre objectif est l’étude de l’influence à long terme de l’environnement périnatal (endocrinien et métabolique) sur le contrôle hypothalamique de l’homéostasie énergétique. As previously described, hypothalamic leptin sensitivity is critical in the control of energy homeostasis and neuronal organization. Previously, we have demonstrated that leptin, insulin, CNTF and serotonin share common signaling pathways. We have showed that both leptin and insulin resistances are associated, linking then obesity to type 2 diabetes through most likely resistin. This part of our project will be organized in the following tasks.

Projets scientifiques
1. Molecular and cellular mechanisms involved in hypothalamic insulin and leptin resistance
* Cellular and molecular mechanisms of resistin/TLR4-dependent hypothalamic nuclei inflammation and insulin resistance
Resistin induces hypothalamic neuro-inflammation (Benomar et al., 2013)

2. Impact of hypothalamic hormonal and metabolic environment during perinatal periods
* Expression profile of hypothalamic microRNA :
According to our previous studies we hypothesize that changes of specific miRNA expression levels may be involved, at least partially, in the process of diet or hormonal induced alteration of hypothalamic neuronal organization during early life. Furthermore, we will continue the improvement this technique by developing a guideline to quantify barcoding impact in multiplex microRNA expression profiles using Illumina technology.

Validation and the physiological relevance of miRNAs.
The characterization of specific miRNAs will be validated by in situ hybridization (ISH) to specifically confirm their localization in specific hypothalamic nuclei.

Validation and the physiological relevance of hypothalamic miRNAs.

Publications choisies

  • Benomar Y, Taouis M. Molecular Mechanisms Underlying Obesity-Induced Hypothalamic Inflammation and Insulin Resistance: Pivotal Role of Resistin/TLR4 Pathways. Front Endocrinol (Lausanne). 2019 Mar 8;10:140. DOI: 10.3389/fendo.2019.00140. eCollection 2019. Review.
  • Le Stunff H, Véret J, Kassis N, Denom J, Meneyrol K, Paul JL, Cruciani-Guglielmacci C, Magnan C, Janel N. Deciphering the Link Between Hyperhomocysteinemia and Ceramide Metabolism in Alzheimer-Type Neurodegeneration. Front Neurol. 2019 Jul 31;10:807. DOI: 10.3389/fneur.2019.00807
  • Poizat G, Alexandre C, Al Rifai S, Riffault L, Crepin D, Benomar Y, Taouis M. Maternal resistin predisposes offspring to hypothalamic inflammation and body weight gain. PLoS One. 2019 Mar 7;14(3):e0213267. DOI: 10.1371/journal.pone.0213267. eCollection 2019.
  • Campana M, Bellini L, Rouch C, Rachdi L, Coant N, Butin N, Bandet CL, Philippe E, Meneyrol K, Kassis N, Dairou J, Hajduch E, Colsch B, Magnan C, Le Stunff H. Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats. Mol Metab. 2018 Feb;8:23-36. DOI: 10.1016/j.molmet.2017.10.013
  • Benoit C, Doubi-Kadmiri S, Benigni X, Crepin D, Riffault L, Poizat G, Vacher CM, Taouis M, Baroin-Tourancheau A, Amar L. miRNA Long-Term Response to Early Metabolic Environmental Challenge in Hypothalamic Arcuate Nucleus. Front Mol Neurosci. 2018 Mar 28;11:90. DOI: 10.3389/fnmol.2018.00090. eCollection 2018.
  • Cruciani-Guglielmacci C, López M, Campana M, le Stunff H. Brain Ceramide Metabolism in the Control of Energy Balance. Front Physiol. 2017 Oct 12;8:787. Review. DOI: 10.3389/fphys.2017.00787
  • Taouis M. MicroRNAs in the hypothalamus. Best Pract Res Clin Endocrinol Metab. 2016 Oct;30(5):641-651. DOI: 10.1016/j.beem.2016.11.006. Epub 2016 Nov 15. Review.
2021

• Tirou L, Russo M, Faure H, Pellegrino G, Demongin C, Daynac M, Sharif A, Amosse J, Le Lay S, Denis R, Luquet S, Taouis M, Benomar Y, Ruat M. Sonic Hedgehog receptor Patched deficiency in astrocytes enhances glucose metabolism in mice. Mol Metab. 2021 May;47:101172. doi: 10.1016/j.molmet.2021.101172. Epub 2021 Jan 26. PMID: 33513436
• Daniel J Klionsky et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8. PMID: 33634751
• Amine H, Benomar Y, Taouis M. Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma. Sci Rep. 2021 Mar 8;11(1):5427. doi: 10.1038/s41598-021-85018-7. PMID: 33686181
• Taouis M, Benomar Y. Is resistin the master link between inflammation and inflammation-related chronic diseases? Mol Cell Endocrinol. 2021 Aug 1;533:111341. doi: 10.1016/j.mce.2021.111341. Epub 2021 May 31. PMID: 34082045
• Meneyrol K, Estévez-Salguero Á, González-García I, Guitton J, Taouis M, Benomar Y, Magnan C, López M, Le Stunff H. Ovarian insufficiency impairs glucose-stimulated insulin secretion through activation of hypothalamic de novo ceramide synthesis. Metabolism. 2021 Oct;123:154846. doi: 10.1016/j.metabol.2021.154846. Epub 2021 Aug 8. PMID: 34371064.
• Hamelin H, Poizat G, Florian C, Kursa MB, Pittaras E, Callebert J, Rampon C, Taouis M, Hamed A, Granon S. Prolonged Consumption of Sweetened Beverages Lastingly Deteriorates Cognitive Functions and Reward Processing in Mice. Cereb Cortex. 2021 Sep 7:bhab274. doi: 10.1093/cercor/bhab274. Online ahead of print. PMID: 34491298
• Magnan C, Le Stunff H. Role of hypothalamic de novo ceramides synthesis in obesity and associated metabolic disorders. Mol Metab. 2021 Nov;53:101298. doi: 10.1016/j.molmet.2021.101298. Epub 2021 Jul 15. PMID: 34273578
• Pineau AM, Vessely R, Le Stunff H. [Is obesity-induced insulin resistance mediated by ceramide C18:0 synthesis de novo in skeletal muscles]. Med Sci (Paris). 2021 Jan;37(1):100-102. doi: 10.1051/medsci/2020264. Epub 2021 Jan 25. PMID: 33492226

2020

• Ghoula M, Le Marec A, Magnan C, Le Stunff H, Taboureau O. Identification of the Interactions Interference Between the PH and START Domain of CERT by Limonoid and HPA Inhibitors. Front Mol Biosci. 2020 Nov 27;7:603983. doi: 10.3389/fmolb.2020.603983. eCollection 2020. PMID: 33330630
• Reginato A, Siqueira BP, Miyamoto JÉ, Portovedo M, Costa SO, de Fante T, Rodrigues HG, Ignácio-Souza LM, Torsoni MA, Torsoni AS, Le Stunff H, Belsham DD, Milanski M. Acute effects of fatty acids on autophagy in NPY neurones. J Neuroendocrinol. 2020 Oct;32(10):e12900. doi: 10.1111/jne.12900. PMID: 33040385.
• Miyamoto JÉ, Reginato A, Portovedo M, Dos Santos RM, Stahl MA, Le Stunff H, Latorraca MQ, de Barros Reis MA, Arantes VC, Doneda DL, Ignacio-Souza LM, Torsoni AS, Grimaldi R, Ribeiro APB, Torsoni MA, Milanski M. Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice. Metabolism. 2020 Nov;112:154350. doi: 10.1016/j.metabol.2020.154350. Epub 2020 Sep 8. PMID: 32910938
• Tan-Chen S, Guitton J, Bourron O, Le Stunff H, Hajduch E. Sphingolipid Metabolism and Signaling in Skeletal Muscle: From Physiology to Physiopathology. Front Endocrinol (Lausanne). 2020 Aug 7;11:491. doi: 10.3389/fendo.2020.00491. eCollection 2020. PMID: 32849282
• Amouyal C, Castel J, Guay C, Lacombe A, Denom J, Migrenne-Li S, Rouault C, Marquet F, Georgiadou E, Stylianides T, Luquet S, Le Stunff H, Scharfmann R, Clément K, Rutter GA, Taboureau O, Magnan C, Regazzi R, Andreelli F. A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice. EBioMedicine. 2020 Aug;58:102895. doi: 10.1016/j.ebiom.2020.102895. Epub 2020 Jul 30. PMID: 32739864
• Guitton J, Bandet CL, Mariko ML, Tan-Chen S, Bourron O, Benomar Y, Hajduch E, Le Stunff H. Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes. Cells. 2020 Jul 13;9(7):1682. doi: 10.3390/cells9071682. PMID: 32668665
• Portovedo M, Reginato A, Miyamoto JÉ, Simino LA, Hakim MP, Campana M, Leal RF, Ignácio-Souza LM, Torsoni MA, Magnan C, Le Stunff H, Torsoni AS, Milanski M. Lipid excess affects chaperone-mediated autophagy in hypothalamus. Biochimie. 2020 Sep;176:110-116. doi: 10.1016/j.biochi.2020.06.008. Epub 2020 Jul 2. PMID: 32623049
• Oshima M, Pechberty S, Bellini L, Göpel SO, Campana M, Rouch C, Dairou J, Cosentino C, Fantuzzi F, Toivonen S, Marchetti P, Magnan C, Cnop M, Le Stunff H, Scharfmann R. Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity. Diabetologia. 2020 Feb;63(2):395-409. doi: 10.1007/s00125-019-05046-x. Epub 2019 Dec 3. PMID: 31796987

2019

• Taouis M, Torres-Aleman I. Editorial: Insulin and The Brain. Front Endocrinol (Lausanne). 2019 May 10;10:299. doi: 10.3389/fendo.2019.00299. eCollection 2019. PMID: 31133989
• Benomar Y, Taouis M. Molecular Mechanisms Underlying Obesity-Induced Hypothalamic Inflammation and Insulin Resistance: Pivotal Role of Resistin/TLR4 Pathways. Front Endocrinol (Lausanne). 2019 Mar 8;10:140. doi: 10.3389/fendo.2019.00140. eCollection 2019. Review.PMID: 30906281
• Le Stunff H, Véret J, Kassis N, Denom J, Meneyrol K, Paul JL, Cruciani-Guglielmacci C, Magnan C, Janel N. Deciphering the Link Between Hyperhomocysteinemia and Ceramide Metabolism in Alzheimer-Type Neurodegeneration. Front Neurol. 2019 Jul 31;10:807. doi: 10.3389/fneur.2019.00807.
• Poizat G, Alexandre C, Al Rifai S, Riffault L, Crepin D, Benomar Y, Taouis M. Maternal resistin predisposes offspring to hypothalamic inflammation and body weight gain. PLoS One. 2019 Mar 7;14(3):e0213267. doi: 10.1371/journal.pone.0213267. eCollection 2019. PMID: 30845245

2018

• Bandet CL, Mahfouz R, Véret J, Sotiropoulos A, Poirier M, Giussani P, Campana M, Philippe E, Blachnio-Zabielska A, Ballaire R, Le Liepvre X, Bourron O, Berkeš D, Górski J, Ferré P, Le Stunff H, Foufelle F, Hajduch E. Ceramide Transporter CERT Is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions. Diabetes. 2018 Jul;67(7):1258-1271. doi: 10.2337/db17-0901. Epub 2018 May 14. PMID: 29759974
• González-García I, Contreras C, Estévez-Salguero Á, Ruíz-Pino F, Colsh B, Pensado I, Liñares-Pose L, Rial-Pensado E, Martínez de Morentin PB, Fernø J, Diéguez C, Nogueiras R, Le Stunff H, Magnan C, Tena-Sempere M, López M. Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress. Cell Rep. 2018 Oct 9;25(2):413-423.e5. doi: 10.1016/j.celrep.2018.09.038. PMID: 30304681
• Miao J, Benomar Y, Al Rifai S, Poizat G, Riffault L, Crépin D, Taouis M. Resistin inhibits neuronal autophagy through Toll-like receptor 4. J Endocrinol. 2018 Jul;238(1):77-89. doi: 10.1530/JOE-18-0096. Epub 2018 May 17. PMID: 29773580
• Campana M, Bellini L, Rouch C, Rachdi L, Coant N, Butin N, Bandet CL, Philippe E, Meneyrol K, Kassis N, Dairou J, Hajduch E, Colsch B, Magnan C, Le Stunff H. Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats. Mol Metab. 2018 Feb;8:23-36. doi: 10.1016.
• Benoit C, Doubi-Kadmiri S, Benigni X, Crepin D, Riffault L, Poizat G, Vacher CM, Taouis M, Baroin-Tourancheau A, Amar L. miRNA Long-Term Response to Early Metabolic Environmental Challenge in Hypothalamic Arcuate Nucleus. Front Mol Neurosci. 2018 Mar 28;11:90. doi: 10.3389/fnmol.2018.00090. eCollection 2018. PMID: 29643765

2017

• Cruciani-Guglielmacci C, López M, Campana M, le Stunff H. Brain Ceramide Metabolism in the Control of Energy Balance. Front Physiol. 2017 Oct 12;8:787. doi:10.338. Review.PMID: 29075199
• Cruciani-Guglielmacci C, Bellini L, Denom J, Oshima M, Fernandez N, Normandie-Levi P, Berney XP, Kassis N, Rouch C, Dairou J, Gorman T, Smith DM, Marley A, Liechti R, Kuznetsov D, Wigger L, Burdet F, Lefèvre AL, Wehrle I, Uphues I, Hildebrandt T, Rust W, Bernard C, Ktorza A, Rutter GA, Scharfmann R, Xenarios I, Le Stunff H, Thorens B, Magnan C, Ibberson M. Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for Elovl2 in glucose-induced insulin secretion. Mol Metab. 2017 Jan 26;6(4):340-351. doi: 10.1016.
• Wigger L, Cruciani-Guglielmacci C, Nicolas A, Denom J, Fernandez N, Fumeron F, Marques-Vidal P, Ktorza A, Kramer W, Schulte A, Le Stunff H, Liechti R, Xenarios I, Vollenweider P, Waeber G, Uphues I, Roussel R, Magnan C, Ibberson M, Thorens B. Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans. Cell Rep. 2017 Feb 28;18(9):2269-2279. doi: 10.1016/j.celrep.2017.02.019.

2016

• Taouis M. MicroRNAs in the hypothalamus. Best Pract Res Clin Endocrinol Metab. 2016 Oct;30(5):641-651. doi: 10.1016/j.beem.2016.11.006. Epub 2016 Nov 15. Review.
• Doubi-Kadmiri S, Benoit C, Benigni X, Beaumont G, Vacher CM, Taouis M, Baroin-Tourancheau A, Amar L. Substantial and robust changes in microRNA transcriptome support postnatal development of the hypothalamus in rat. Sci Rep. 2016 Apr 27;6:24896. doi: 10.1038/srep24896.PMID: 271184
• Benomar Y, Amine H, Crépin D, Al Rifai S, Riffault L, Gertler A, Taouis M. Central Resistin/TLR4 Impairs Adiponectin Signaling, Contributing to Insulin and FGF21 Resistance. Diabetes. 2016 Apr;65(4):913-26. doi: 10.2337/db15-1029. Epub 2016 Jan 6.

2015

• Ould Hamouda H, Delplanque B, Benomar Y, Crépin D, Riffault L, LeRuyet P, Bonhomme C, Taouis M. Milk-soluble formula increases food intake and reduces Il6 expression in elderly rat hypothalami. J Endocrinol. 2015 Jul;226(1):67-80. doi: 10.1530/JOE-15-0076. Epub 2015 May 20. PMID: 25994005
• Papazoglou IK, Jean A, Gertler A, Taouis M, Vacher CM. Hippocampal GSK3β as a Molecular Link Between Obesity and Depression. Mol Neurobiol. 2015 Aug;52(1):363-74. doi: 10.1007/s12035-014-8863-x. Epub 2014 Aug 29. PMID: 25169083
• Crépin D, Benomar Y, Riffault L, Amine H, Gertler A, Taouis M. The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment. Mol Cell Endocrinol. 2014 Mar 25;384(1-2):1-11. doi: 10.1016/j.mce.2013.12.016. Epub 2014 Jan 4.

2014

• Tchankouo-Nguetcheu S, Udinotti M, Durand M, Meng TC, Taouis M, Rabinow L. Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B. Mol Genet Genomics. 2014 Oct ;289(5):795-806.
• Baroin-Tourancheau A, Benigni X, Benoit C, Doubi-Kadmiri S, Vacher CM, Taouis M, Amar L. Keys for microRNA expression profiling of single rat hypothalamic nuclei and multiplex sequencing strategies. Exp Physiol. 2014 Jan ;99(1):72-7.
• Crépin D, Benomar Y, Riffault L, Amine H, Gertler A, Taouis M. The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment. Mol Cell Endocrinol. 2014 Mar 25 ;384(1-2):1-11.

2013

• Benomar Y, Gertler A, De Lacy P, Crépin D, Hamouda HO, Riffault L and Taouis M.(2013)Central Resistin Overexposure Induces Insulin Resistance Through Toll-like Receptor 4. Diabetes 62:102-14.
• Benoit C, Ould-Hamouda H, Crepin D, Gertler A, Amar L, Taouis M.(2013) Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs. J Endocrinol. 218:35-47

2012

• Amar L, Benoit C, Beaumont G, Vacher CM, Crepin D, Taouis M, Baroin-Tourancheau A (2012) MicroRNA expression profiling in hypothalamic arcuate and paraventricular nuclei from single rats using Illumina sequencing technology . Journal of neurosciences methods. 209 : 134-143.
• Sartorius T, Heni M, Tschritter O, Preissl H, Hopp S, Fritsche A, Lievertz PS, Gertler A, Berthou F, Taouis M, Staiger H, Häring HU, Hennige AM. (2012) Leptin affects insulin action in astrocytes and impairs insulin-mediated physical activity. Cell Physiol Biochem.30:238-46.
• Papazoglou I, Berthou F, Vicaire N, Rouch C, Markaki EM, Bailbe D, Portha B, Taouis M, Gerozissis K. (2012) Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model. Mol Cell Endocrinol. 35:136-44.
• Couvreur O, Aubourg A, Crépin D, Degrouard J, Gertler A, Taouis M, Vacher CM. (2012) The anorexigenic cytokine Ciliary Neurotrophic Factor (CNTF) stimulates POMC gene expression via receptors localized in the nucleus of arcuate neurons. Am J Physiol Endocrinol Metab. 302:E458-67.

2011

• Couvreur O, Ferezou J, Gripois D, Serougne C, Crépin D, Aubourg A, Gertler A, Vacher CM, Taouis M. (2011) Unexpected long-term protection of adult offspring born to high-fat fed dams against obesity induced by a sucrose-rich diet. PLoS One.6(3):e18043.
• Berthou F, Rouch C, Gertler A, Gerozissis K, Taouis M. (2011) Chronic central leptin infusion differently modulates brain and liver insulin signaling. Mol Cell Endocrinol. 30 ;337(1-2):89-95.