Presentation of the research topic

Obesity and its metabolic complications are a major global health challenge. It has long been accepted that weight loss is the most effective therapeutic strategy to combat conditions such as type-2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Recent and emerging pharmacological strategies have shown promise in this area, however, with nearly 25% of the global population affected by obesity, the sheer scale of the problem remains daunting. It is also becoming clear that weight loss following prior obesity does not completely reverse certain aspects of the organ physiology. In the LivAdip team, we focus on the role of the liver-adipose tissue dialog in the context of obesity, and aim to understand the changes in these tissues in the pathogenesis of obesity and MASLD and the mechanisms of disease regression or persistence following weight loss.

Key-words

Obesity ; MASLD ; Adipose Tissue ; Liver

Joel Haas

Research director Inserm, Group Leader

ORCID : 0000-0002-0028-5988

I am a full-time INSERM research director with extensive experience studying glucose and lipid metabolism in the context of cardiometabolic disease. Prior to my PhD, I worked as a research associate at the Joslin Diabetes Center at Harvard Medical School studying the contribution of defective hepatic insulin signaling to complications of type-2 diabetes. I then obtained a PhD in biochemistry and molecular biology at the University of California-San Francisco, studying the physiological roles of triglyceride synthesizing enzymes (DGAT1 and DGAT2). In 2013, I joined the INSERM laboratory UMR1011 in Lille, (Nuclear Receptors, Metabolic and Cardiovascular Diseases) for a post-doctoral fellowship and in 2019 I was obtained a full-time tenured researcher position in the same department. I currently co-lead an emerging team entitled “LivAdip: Liver and Adipose Tissue Physiomics in Metabolic Disease” with Dr. Delphine Eberlé. I have obtained numerous prestigious awards including the EMBO Long Term Fellowship, French ANR Young Researcher Grant, and an ERC Starting grant. My main research project focuses on how metabolic factors impact the function of the innate immune system in pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD).

Delphine Eberlé

Associate professor, Lille University, Group leader

ORCID : 0000-0003-2211-6146

I am an associate professor in Physiology at Lille University. I am particularly interested in exploring the role of adipose tissue plasticity in the context of obesity and its associated complications MASLD (Metabolic dysfunction-associated steatotic liver disease). Passionate about human nutrition, I began my scientific journey at the École Nationale Supérieure d'Agronomie in Rennes, earning an engineering degree in Agronomy with a focus on Biochemistry and Genetics. I obtained my PhD in Paris studying the genetics of obesity, with a focus on the lipogenic transcription factor SREBP-1. I then completed postdoctoral trainings at the Joslin Diabetes Center in Boston and at the University of California-San Francisco (USA), where I focused on mechanisms of inflammation development and resolution in obesity and atherosclerosis. In 2013, I joined the Biology Department at the Faculty of Science and Technology at Lille University as an Associate Professor, and led studies on the developmental programming of adipose tissue and obesity, particularly how early postnatal nutrition influence long-term metabolic health via epigenetic mechanisms. In 2020, I joined the UMR1011 research unit and the European Genomic Institute for Diabetes (EGID), to continue my research on adipose tissue function in metabolic diseases. I currently co-direct the thematic group LivAdiP, focusing on liver-adipose tissue crosstalk in obesity and MASLD combining multidisciplinary approaches from omics to physiology. Since 2024, I have served as Vice President of AFERO, the French Association for Studies and Research on Obesity.

Viktor Liénard

Ph.D student, Lille University

ORCID : 0009-0002-3449-8452

After obtaining a Master's degree in Biology-Health (Precision Health pathway), Viktor joined UMR1011 to carry out a thesis on the mechanisms involved in the development of MASLD. His work focuses in particular on the influence of Apolipoprotein F deficiency on the progression of the disease, as well as the impact of major genetic variants (PNPLA3 I148M, TM6SF2 E167K) on its development.

Pauline JACQUEMAIN

Engineer, INSERM

ORCID : 0000-0003-1836-9677

Pauline Jacquemain graduated from Polytech Lille in 2020 with a degree in Biological and Food Engineering. At the end of her studies, she joined UMR1011, headed by Prof. Bart Staels, and more specifically team 1 under the direction of Dr. Joel Haas. As part of the ERC Metabo3DC project, the team is working on the metabolic activation of dendritic cells in MASH. It is involved in in vitro and in vivo experiments, manages a technical platform and is a first-aid worker.

 

Camilla KLAIMI

Ph.D student, Lille University

Camilla Klaimi, PhD candidate at the University of Lille, specialising in immunometabolism with a focus on the metabolic reprogramming of dendritic cells in steatotic liver disease associated with metabolic dysfunction (SAMLD).

 

Anne-Sophie JENEQUIN

Research Engineer in mass spectrometry, INSERM

ORCID : 0009-0003-6205-0409

Anne-Sophie obtained a Master's degree in Biotechnology in 2020, and began her career as a Research Engineer in analytical chemistry, specializing in HPLC-MS/MS, at the Institut Charles Viollette in Villeneuve d’Ascq, FR. Her primary mission was to identify molecules with antibacterial properties, aiming to propose new classes of drugs capable of combating bacteria resistant to existing treatments. Subsequently, she worked in the private sector as a Laboratory Technician specializing in metabolomic studies at Aliri, where she utilized her chromatography skills for high-precision analyses and collaborated with various companies. Finally, she joined the LivAdip team in the department UMR1011as a Research Engineer in analytical chemistry, specializing in HPLC-MS/MS analyses. Her role involves developing an MS platform to conduct metabolomic analyses in close collaboration with research groups

Audrey DUPRE

Ph.D student, Lille University

After earning a Bachelor's degree in Cellular Biology and Physiology, followed by a Master's degree in Biology and Health at the University of Lille, I passed the entrance exam for the Lille doctoral school to pursue a PhD. I am now working under the supervision of Dr. Delphine Eberlé on the role of Rora in mature adipocytes and metabolic homeostasis within Unit U1011, led by Bart Staels, which focuses on nuclear receptors and their impact on metabolic and cardiovascular diseases.

Emilie CADART

Engineer, Lille University

After earning a Bachelor's degree in Life Sciences, with a focus on Biology and Biochemistry, at the University of Sciences Jean Perrin in Lens, I pursued a Master's degree in Biology and Health, specializing in Fundamental and Clinical Oncology. I then held a position as a research engineer at UGSF UMR 8576 for one year before joining the U1011 unit, within Bart Staels' team, as an assistant engineer.

Ghania KARA-ALI

Postdoctoral fellow, Lille University

ORCID : 0000-0003-4004-7551

Ghania Kara-Ali is a postdoctoral researcher specializing in metabolic dysfunctions with a focus on liver and adipose tissue physiopathology. She completed her PhD in 2022, where she studied the development of hepatocellular carcinoma in the context of metabolic-associated steatohepatitis and diabetes. Currently, her research explores the impact of weight loss on adipose tissue and liver remodeling in obesity.

Marine HUILLET

Postdoctoral fellow, INSERM

ORCID : 0000-0002-6508-4351

Passionate about biology, I obtained my bachelor's degree in cellular biology and physiology in 2017, as well as a master's degree in physiopathology in 2019. Following that, I began my PhD, co-supervised by Drs. Sandrine Ellero-Simatos and Nicolas Loiseau, during which we studied the sex-dependent and gut microbiota-dependent role of the constitutive androstane receptor (CAR) in the development of metabolic dysfunction-associated liver diseases. In August 2024, I joined U1011 as a postdoctoral researcher to better understand the role of dendritic cells in the development of metabolic dysfunction-associated liver diseases.

Arthur GRENON

Engineer, Lille University

ORCID : 0009-0009-3717-1341

  • Project manager (APTEEUS) during 2 years: Development of in vitro phenotypical tests for high-throughput screening of repurposable molecules
  • Study engineer (UMR1011): Involved in scRNAseq project (EvoLiLiD), sc/snRNAseq libraries preparation and scRNAseq analysis

LivAdip group from UMR1011 developped lot of scientific skills :

  • Single Cell/Single Nuclei RNAseq (10X Chromium)
  • LCMS Metabolomics (Bruker TimsTOF Pro2)
  • Metabolic Cages (Sable Systems Promethion)
  • Seahorse Extracellular Flux Analyzer

List of main publications from LivAdip group:

Johanns M, Haas JT, Raverdy V, Vandel J, Chevalier-Dubois J, Guille L, Derudas B, Legendre B, Caiazzo R, Verkindt H, Gnemmi V, Leteurtre E, Derhourhi M, Bonnefond A, Froguel P, Eeckhoute J, Lassailly G, Mathurin P, Pattou F, Staels B, Lefebvre P. Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.  JHEP Rep. 2023 Oct 27;6(1):100948. PMID: 38125300

Deprince A, Hennuyer N, Kooijman S, Pronk ACM, Baugé E, Lienard V, Verrijken A, Dirinck E, Vonghia L, Woitrain E, Kloosterhuis NJ, Marez E, Jacquemain P, Wolters JC, Lalloyer F, Eberlé D, Quemener S, Vallez E, Tailleux A, Kouach M, Goossens JF, Raverdy V, Derudas B, Kuivenhoven JA, Croyal M, van de Sluis B, Francque S, Pattou F, Rensen PCN, Staels B*, Haas JT*#. Apolipoprotein F Is Reduced in Humans with Steatosis and Controls Plasma Triglyceride-Rich Lipoprotein Metabolism. Hepatology 2023 Jun 23 *Co-supervising authors, #Corresponding Author

Butruille L*, Marousez L*, Pourpe C, Oger F, Lecoutre S, Catheline D, Görs S, Metges CC, Guinez C, Laborie C, Deruelle P, Eeckhoute J, Breton C, Legrand P, Lesage J, Eberlé D. Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring. Int J Obes (Lond). 2019 Dec;43(12):2381-2393.

Grzych G, Chávez-Talavera O, Descat A, Thuillier D, Verrijken A, Kouach M, Legry V, Verkindt H, Raverdy V, Legendre B, Caiazzo R, Van Gaal L, Goossens JF, Paumelle R, Francque S, Pattou F, Haas JT*, Tailleux A*, Staels B*#. NASH-related increases in plasma bile acid levels depend on insulin resistance. JHEP Rep. 2020 Dec 16;3(2):100222., *Co-supervising authors, #Corresponding Author

Marousez L.*, Hanssens S*., Butruille L., Petit C., Pourpe C., Besangez C., Rakza L., Storme L., Deruelle P., Lesage J., and Eberlé D. Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation. International Journal of Obesity. 2021, 45(5):1052-1060

Haas JT*, Vonghia L*, Mogilenko DM*, Verrijken A, Molendi-Coste O, Fleury S, Deprince A, Nikitin A, Woitran E, Ducrocq-Geoffroy L, Pic S, Derudas B, Dehondt H, Gheeraert C, van Gaal L, Driessen A, Lefebvre P, Staels B#, Francque S#, Dombrowicz D# Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nature Metabolism, 1, 2019 Jun;1(6):604-614  * Co-first authors

List of fundings obtained by LivAdip group:

 

Dr Delphine EBERLE, Associate professor
delphine.eberle[chez]univ-lille[point].fr

Dr Joel HAAS, Research director
joel.haas[chez]pasteur-lille[point].fr