Faculty of Biological Sciences

Dr Beatrice Maria Filippi

PhD
UAF in Neuroscience
School of Biomedical Sciences

Contact:  Garstang 6.41e, +44(0) 113 34 34424, email address for  

Research Interests

How Insulin resistance in the brain affects the metabolic behaviour and favours neurodegeneration.

Diabetes and obesity are epidemic diseases that are rising among the world population. Eight out of 10 men and almost 7 in 10 women will be overweight or obese by 2020 1. Most of these overweight/obese individuals are more prone to develop insulin resistance and diabetes. Overnutrition is the predominant pathogenic inducer of insulin resistance, which is mainly caused by increased circulating levels of glucose, free fatty acid (FFA) and amino acids 2,3. Increase of these circulating factors causes intracellular stresses such as mitochondrial oxidative stress and endoplasmic reticulum (ER) stress, which occur both in peripheral tissues 4 and in the Central Nervous System (CNS) 5. The CNS collects peripheral inputs to regulate the metabolic status of an individual and signals back to the periphery in order to keep a metabolic homeostasis. Any alteration of these processes can lead to a metabolic disease and vice versa. Since overnutrition affects the CNS regulatory functions, restoring the brain’s ability to modulate metabolic functions could be very important to overcome a pathological condition.

 

Faculty Research and Innovation

Postgraduates

Bianca Patel (Primary supervisor) 50% FTE

Filippi BM, Abraham MA, Silva PN, Rasti M, LaPierre MP, Bauer PV, Rocheleau JV, Lam TKT Dynamin-Related Protein 1-Dependent Mitochondrial Fission Changes in the Dorsal Vagal Complex Regulate Insulin Action CELL REPORTS 18 2301-2309, 2017
DOI:10.1016/j.celrep.2017.02.035

Zadeh-Tahmasebi M, Duca FA, Rasmussen BA, Bauer PV, Côté CD, Filippi BM, Lam TKT Activation of short and long chain fatty acid sensing machinery in the ileum lowers glucose production in vivo Journal of Biological Chemistry 291 8816-8824, 2016
DOI:10.1074/jbc.M116.718460
View abstract

LaPierre MP, Abraham MA, Yue JTY, Filippi BM, Lam TKT Glucagon signalling in the dorsal vagal complex is sufficient and necessary for high-protein feeding to regulate glucose homeostasis in vivo EMBO Reports 16 1299-1307, 2015
DOI:10.15252/embr.201540492
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Côté CD, Rasmussen BA, Duca FA, Zadeh-Tahmasebi M, Baur JA, Daljeet M, Breen DM, Filippi BM, Lam TKT Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats through a neuronal network Nature Medicine 21 498-505, 2015
DOI:10.1038/nm.3821
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Duca FA, Côté CD, Rasmussen BA, Zadeh-Tahmasebi M, Rutter GA, Filippi BM, Lam TKT Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats Nature Medicine 21 506-511, 2015
DOI:10.1038/nm.3787
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Yue JTY, Abraham MA, Lapierre MP, Mighiu PI, Light PE, Filippi BM, Lam TKT A fatty acid-dependent hypothalamic-DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins Nature Communications 6 -, 2015
DOI:10.1038/ncomms6970
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LaPierre MP, Abraham MA, Filippi BM, Yue JTY, Lam TKT Glucagon and lipid signaling in the hypothalamus Mammalian Genome 25 434-441, 2014
DOI:10.1007/s00335-014-9510-6
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Rasmussen BA, Breen DM, Duca FA, Côté CD, Zadeh-Tahmasebi M, Filippi BM, Lam TKT Erratum: Jejunal leptin-PI3K signaling lowers glucose production (Cell Metabolism (2013) 19 (155-161)) Cell Metabolism 19 548-, 2014
DOI:10.1016/j.cmet.2014.02.005

Filippi BM, Bassiri A, Abraham MA, Duca FA, Yue JTYY, Lam TKT Insulin signals through the dorsal vagal complex to regulate energy balance Diabetes 63 892-899, 2014
DOI:10.2337/db13-1044
View abstract

Filippi BM, Lam TKT Leptin and Aging Aging 6 82-83, 2014

Rasmussen BA, Breen DM, Duca FA, Côté CD, Tahmasebi MZ, Filippi BM, Lam TKT Jejunal leptin-PI3K signaling lowers glucose production Cell Metabolism 19 155-161, 2014
DOI:10.1016/j.cmet.2013.11.014
View abstract

Abraham MA, Filippi BM, Kang GM, Kim MS, Lam TKT Insulin action in the hypothalamus and dorsal vagal complex Experimental Physiology 99 1104-1109, 2014
DOI:10.1113/expphysiol.2014.079962
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Abraham MA, Yue JTY, LaPierre MP, Rutter GA, Light PE, Filippi BM, Lam TKT Hypothalamic glucagon signals through the K<inf>ATP</inf>channels to regulate glucose production Molecular Metabolism 3 202-208, 2014
DOI:10.1016/j.molmet.2013.11.007
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Filippi BM, Abraham MA, Yue JTY, Lam TKT Insulin and glucagon signaling in the central nervous system Reviews in Endocrine and Metabolic Disorders 14 365-375, 2013
DOI:10.1007/s11154-013-9258-4
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Mighiu PI, Yue JTY, Filippi BM, Abraham MA, Chari M, Lam CKL, Yang CS, Christian NR, Charron MJ, Lam TKT Hypothalamic glucagon signaling inhibits hepatic glucose production Nature Medicine 19 766-772, 2013
DOI:10.1038/nm.3115
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Filippi BM, Yang CS, Tang C, Lam TKT Insulin activates Erk1/2 signaling in the dorsal Vagal complex to inhibit glucose production Cell Metabolism 16 500-510, 2012
DOI:10.1016/j.cmet.2012.09.005
View abstract

Mighiu PI, Filippi BM, Lam TKT Linking inflammation to the brain-liver axis Diabetes 61 1350-1352, 2012
DOI:10.2337/db12-0330

Filippi BM, Mighiu PI, Lam TKT Is insulin action in the brain clinically relevant? Diabetes 61 773-775, 2012
DOI:10.2337/db12-0048

Filippi BM, De Los Heros P, Mehellou Y, Navratilova I, Gourlay R, Deak M, Plater L, Toth R, Zeqiraj E, Alessi DR MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases EMBO Journal 30 1730-1741, 2011
DOI:10.1038/emboj.2011.78
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Zeqiraj E, Filippi BM, Deak M, Alessi DR, Van Aalten DMF Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation Science 326 1707-1711, 2009
DOI:10.1126/science.1178377
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Corda D, Zizza P, Varone A, Filippi BM, Mariggiò S The glycerophosphoinositols: Cellular metabolism and biological functions Cellular and Molecular Life Sciences 66 3449-3467, 2009
DOI:10.1007/s00018-009-0113-4
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Zeqiraj E, Filippi BM, Goldie S, Navratilova I, Boudeau J, Deak M, Alessi DR, Van Aalten DMF ATP and MO25α regulate the conformational state of the STRADα pseudokinase and activation of the LKB1 tumour suppressor PLoS Biology 7 -, 2009
DOI:10.1371/journal.pbio.1000126
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Filippi BM, Mariggiò S, Pulvirenti T, Corda D SRC-dependent signalling regulates actin ruffle formation induced by glycerophosphoinositol 4-phosphate Biochimica et Biophysica Acta - Molecular Cell Research 1783 2311-2322, 2008
DOI:10.1016/j.bbamcr.2008.07.021
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Filippi BM, Alessi DR Novel role for the LKB1 pathway in controlling monocarboxylate fuel transporters Journal of Cell Biology 183 7-9, 2008
DOI:10.1083/jcb.200809056
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Mariggiò S, Filippi BM, Iurisci C, Dragani LK, De Falco V, Santoro M, Corda D Cytosolic phospholipase A<inf>2</inf>α regulates cell growth in RET/PTC-transformed thyroid cells Cancer Research 67 11769-11778, 2007
DOI:10.1158/0008-5472.CAN-07-1997
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Mariggiò S, Sebastià J, Filippi BM, Iurisci C, Volonté C, Amadio S, De Falco V, Santoro M, Corda D A novel pathway of cell growth regulation mediated by a PLA<inf>2</inf>α-derived phosphoinositide metabolite FASEB Journal 20 -, 2006
DOI:10.1096/fj.05-5397fje
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Mancini R, Piccolo E, Mariggio' S, Filippi BM, Iurisci C, Pertile P, Berrie CP, Corda D Reorganization of actin cytoskeleton by the phosphoinositide metabolite glycerophosphoinositol 4-phosphate Molecular Biology of the Cell 14 503-515, 2003
DOI:10.1091/mbc.E02-04-0179
View abstract

Mariggio S, Filippi BM, Iurisci C, Corda D Biological activities of the phosphoinositide derivatives, the glycerophosphoinositols, 2003