Lab Recent Publications

Short chain fatty acids: the messengers from down below 18 August 2023

Virginie Mansuy-Aubert and Yann Ravussin

Short-chain fatty acids (SCFAs), produced by the metabolism of dietary fibers in the gut, have wide-ranging effects locally and throughout the body. They modulate the enteric and central nervous systems, benefit anti-inflammatory pathways, and serve as energy sources. Recent research reveals SCFAs as crucial communicators between the gut and brain, forming the gut-brain axis. This perspective highlights key findings and discusses signaling mechanisms connecting SCFAs to the brain. By shedding light on this link, the perspective aims to inspire innovative research in this rapidly developing field.

Comparison of western diet-induced obesity and streptozotocin mouse models: insights into energy balance, somatosensory dysfunction, and cardiac autonomic neuropathy. 4 June 2024

Elshareif N, Gornick E, Gavini CK, Aubert G, Mansuy-Aubert V.

Front Physiol. 2023 Oct 11;14:1238120. doi: 10.3389/fphys.2023.1238120. PMID: 37885804; PMCID: PMC10598778.

Elshareif N, Gornick E, Gavini CK, Aubert G, Mansuy-Aubert V.

In our research, we thoroughly characterized energy balance and glucose homeostasis, as well as allodynia and cardiac function, all of which have been previously shown to be altered by WD feeding. Notably, our findings revealed that the treatment of WD-fed mice with STZ exacerbated dysfunction in glucose homeostasis via reduced insulin secretion in addition to impaired peripheral insulin signaling. Furthermore, both WD and WD + STZ mice exhibited the same degree of cardiac autonomic neuropathy, such as reduced heart rate variability and decreased protein levels of cardiac autonomic markers. Furthermore, both groups developed the same symptoms of neuropathic pain, accompanied by elevated levels of activating transcription factor 3 (Atf3) in the dorsal root ganglia. These discoveries enhance our understanding of metabolic activity, insulin resistance, neuropathy, and cardiac dysfunction of diet-induced models of obesity and diabetes.

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

LXR agonist modifies neuronal lipid homeostasis and decreases PGD2 in the dorsal root ganglia in western diet-fed mice 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.

Editorial: Neural Control of Energy Homeostasis and Energy Homeostasis Regulation of Brain Function 1 May 2022

Editorial on the Research Topic
Neural Control of Energy Homeostasis and Energy Homeostasis Regulation of Brain Function

Communication between the gut microbiota and peripheral nervous system in health and chronic disease 1 May 2022

Tyler Cook, Virginie M. Aubert

Vagal free fatty acid receptor (FFAR3), is necessary for normal feeding behavior 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.

Fecal Transplantation and Butyrate Improve Neuropathic Pain, Modify PNS Immune Cell Profile, and Lead to DRG and SN Gene Reprogramming 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.

LXR agonist Prevents Peripheral Neuropathy and modifies PNS immune cells in Aged Mice 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.

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.

GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation 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.

CEBPβ regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth 21 June 2023

Mohamad-Reza Aghanoori, Prasoon Agarwal, Evan Gauvin, Raghu S. Nagalingam, Raiza Bonomo, Vinith Yathindranath, Darrell R. Smith, Yan Hai, Samantha Lee, Corinne G. Jolivalt, Nigel A. Calcutt, Meaghan J. Jones, Michael P. Czubryt, Donald W. Miller, Vernon W. Dolinsky, Virginie Mansuy-Aubert & Paul Fernyhough

We hypothesized that impaired autocrine/paracrine actions of IGF-1 in DRG neurons contribute to progressive diabetic sensory neuropathy and therefore investigated the origin of endogenous IGF-1, its regulation at the transcriptional level and the mechanism of suppression of IGF-1 under hyperglycemic conditions in DRG-derived sensory neurons.

Monitoring of Inflammation Reveals Tissue and Sex-specific Responses to Western Diet and Butyrate treatment 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.

Loss of C2-domain protein (C2CD5) Alters Hypothalamic Mitochondrial Trafficking, Structure, and Function 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.

Hypothalamic C2-domain protein involved in MC4R trafficking and control of energy balance 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.

The lipid sensor LXRs protect small sensory neurons from ER stress in early type II diabetic neuropathy 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.

Neuronal LXR Regulates Neuregulin 1 Expression and Sciatic Nerve-Associated Cell Signaling in Western Diet-fed Rodents. 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.