Lab Recent Publications

Since 2016, the MAlab identifies how obesity and diet impacts sensory neurons and physiology

Fecal microbiome transplantation and tributyrin improves early cardiac... 2 March 2023

Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model

More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.

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LXR agonist modifies neuronal lipid homeostasis and decreases... 12 October 2022

GW3965 decreased prostaglandin levels and decreased free fatty acid content, while increasing lysophosphatidylcholine, phosphatidylcholine, and cholesterol ester species in the sensory neurons of the dorsal root ganglia (DRG). These data suggest novel downstream interplaying mechanisms that modifies DRG neuronal lipid following GW3965 treatment.

 

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Communication between the gut microbiota and peripheral nervous... 1 May 2022

Tyler Cook, Virginie M. Aubert

 In this review, we cover the general anatomy and function of the PNS, and then we discuss how the molecules secreted or stimulated by gut microbes signal through the PNS to alter host development and physiology.

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LXR agonist Prevents Peripheral Neuropathy and modifies PNS... 22 February 2022

Chaitanya K. Gavini, Nadia Elshareif, Anand V. Germanwala, Gregory Aubert, Nigel A. Calcutt, Virginie Mansuy-Aubert

Our results suggest that activation of the LXR may block the progression of neuropathy associated with aging by modifying nerve-immune cell cholesterol, thereby providing new pathways to target in efforts to delay neuropathy during aging.

 

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Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms 26 February 2022

In this review, we focus on interventions and their mechanisms that are shown to ameliorate neuropathy in MetS obese models including: (i) inhibition of a sensory neuron population, (ii), modification of dietary components, (iii) activation of nuclear and mitochondrial lipid pathways, (iv) exercise, (v) modulation of gut microbiome composition and their metabolites.

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GnRH neurons recruit astrocytes in infancy to facilitate... 24 January 2022

Giuliana Pellegrino, Marion Martin, Cécile Allet, Tori Lhomme, Sarah Geller, Delphine Franssen, Virginie Mansuy, Maria Manfredi-Lozano, Adrian Coutteau-Robles, Virginia Delli, S. Rasika, Danièle Mazur, Anne Loyens, Manuel Tena-Sempere, Juergen Siepmann, François P. Pralong, Philippe Ciofi, Gabriel Corfas, Anne-Simone Parent, Sergio R. Ojeda, Ariane Sharif & Vincent Prevot

These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation.

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Vagal free fatty acid receptor (FFAR3), is necessary... 30 September 2021

Tyler M. Cook, Chaitanya K. Gavini, Jason Jesse, Gregory Aubert, Emily Gornick, Raiza Bonomo, Laurent Gautron, Brian T. Layden, Virginie Mansuy-Aubert

Our data demonstrate that FFAR3 expressed in vagal neurons regulates feeding behavior and mediates propionate-induced decrease in food intake.

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Monitoring of Inflammation Reveals Tissue and Sex-specific Responses... 30 May 2022

Raiza Bonomo, Sarah Talley, Jomana Hatahet, Chaitanya Gavini, Tyler Cook, Ben Chun, Pete Kekenes-Huskey, Gregory Aubert, Edward Campbell, Virginie Mansuy-Aubert

We observed tissue- and sex- specific caspase-1 activation patterns in obese mice and treated with butyrate. Our work utilizing a caspase-1 biosensor mouse model, flow cytometry and computational analyses and offers new mechanistic insights underlying the effect of butyrate in obesity and its complications.

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Fecal Transplantation and Butyrate Improve Neuropathic Pain, Modify... 15 October 2020

Raiza R. Bonomo, Tyler M. Cook, Chaitanya K. Gavini, Chelsea R. White, Jacob R. Jones, Elisa Bovo, Chelsea White,Raiza R. Bonomo, Tyler M. Cook, aiza R. Bonomo, Tyler M. Cook, Chaitanya K. Gavini, Chelsea R. White, Jacob R. Jones, Elisa Bovo, Chelsea White,Raiza R. Bonomo, Tyler M. Cook

Circulating butyrate, a metabolite secreted by gut microbiome and absorbed in the blood stream, may be involved by acting directly on peripheral nerve system immune cells and gene expression or pain channels.

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Loss of C2-domain protein (C2CD5) Alters Hypothalamic Mitochondrial... 15 May 2021

C. Gavini, C. White, V.M. Aubert and G. Aubert

C2CD5 is a new protein necessary for normal mitochondrial function in the hypothalamus. Its loss alters mitochondrial ultrastructure, localization, and activity within the hypothalamic neurons. C2CD5 may represent a new protein linking hypothalamic dysfunction, mitochondria, and obesity.

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Hypothalamic C2-domain protein involved in MC4R trafficking and... 29 September 2019

Chaitanya Gavini, Tyler Cook, David Rademacher and Virginie Mansuy-Aubert

Hypothalamic C2CD5 is involved in MC4R endocytosis and regulate bodyweight homeostasis. These studies suggest that C2CD5 represents a new protein regulated by metabolic cues and involved in metabolic receptor endocytosis. C2CD5 represent a new target and pathway that could be targeted in Obesity.

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The lipid sensor LXRs protect small sensory neurons... 29 September 2018

Chaitanya Gavini, Raiza Bonomo, Laurent Gautron, Angie Bookout, Syann Lee and Virginie Mansuy-Aubert

Our findings suggest that lipid-binding nuclear receptors expressed in the sensory neurons of the DRG play a role in the onset of obesity-induced hypersensitivity. The LXR and lipid-sensor pathways represent a research avenue to identify targets to prevent debilitating complications affecting the peripheral nerve system in obesity.

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Neuronal LXR Regulates Neuregulin 1 Expression and Sciatic... 17 April 2020

Gavini CK, Bonomo R, Mansuy-Aubert V

Neuronal LXRs may regulate non-neuronal cell function via a Nrg1-dependent mechanism. The decrease in Nrg1 expression in DRG neurons of WD-fed mice may suggest an altered Nrg1-dependent neuron-SC communication in Obesity. The communication between neurons and non-neuronal cells such as SC could be a new biological pathway to study and understand the molecular and cellular mechanism underlying Obesity-associated neuropathy and PNS dysfunction.

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