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Adipocyte dysfunction and metabolic diseases

Xavier Prieur

Investigators: Simon Ducheix, Xavier Prieur, Samy Hadjadj, Jean-Noël Trochu, Matthieu Wargny
PhD students:  Emilie Charon, Marie Palard
Support staff: Gilliane Chadeuf


Obesity is tightly associated with cardiometabolic multimorbidity. Growing evidence supports that adipocyte dysfunction is central to the development of these obesity-related metabolic complications. Although several factors have been highlighted, how do adipocytes become dysfunctional remains a key issue. In addition, the mechanisms linking adipose tissue failure and the cardiometabolic complications associated with obesity, such as insulin resistance, diabetes and its long-term complications, hepatic diseases and heart failure, remain not completely understood. A better comprehension of the pathways controlling adipocyte homoeostasis is crucial to decipher the multiple mechanisms by which adipocytes become dysfunctional.

To this purpose, as a model of adipocyte dysfunction, our group has been studying the pathophysiology of the most severe form of lipodystrophy (nearly complete lack of adipose tissue), the Berardinelli-Seip lipodystrophy (BSCL). In 50% of the cases, BSCL is caused by loss of function mutations in the gene BSCL2, which encodes Seipin, an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue. Our research aims to unravel the role of Seipin in mature adipocyte and to highlight the molecular mechanism involved in the associated cardiometabolic complication with a specific focus on cardiomyopathy.

In addition, aiming to identify new factors that could be involved in the development of adipocyte dysfunction, we highlighted that cholesterol levels were increased in adipose tissue from HFD fed mice. We have demonstrated that cholesterol induces adipocyte dysfunction. Our goal is to unravel the cellular pathway involved in the deleterious effect of cholesterol overload in adipocyte and to correct them with original pharmacological and nutritional interventions.

Learn more about our projects :

Publications


Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort. Wargny M, Croyal M, Ragot S, Gand E, Jacobi D, Trochu J-N, Prieur X, Le May C, Goronflot T, Cariou B, Saulnier P-J, Hadjadj S, SURDIAGENE study group. Cardiovasc Diabetol 21: 101, 2022. doi: 10.1186/s12933-022-01505-9.

Seipin localizes at endoplasmic reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes. Y Combot, V T Salo, G Chadeuf, MHölttä, K Ven, I Pulli, S Ducheix, C Pecqueur, O Renoult, B Lak6, S Li2,3, L Karhinen2,3, I Belevich7, C Le May1, J Rieusset, S Le Lay, Mikael Croyal, K Si Tayeb, H Vihinen, E Jokitalo, K Törnquist, C Vigouroux, B Cariou, J Magré, A Larhlimi, E Ikonen, X Prieur; Cell reports 38, 110213, doi:10.1016/j.celrep.2021.110213 (2021)

The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Cardiomyopathy in a Diabetic Lipodystrophic Mouse Model. Joubert M, Jagu B, Montaigne D, Marechal X, Tesse A, Ayer A, Dollet L, Le May C, Toumaniantz G, Manrique A, Charpentier F, Staels B, Magré J, Cariou B, Prieur X. Diabetes 2017;66:1030–1040.

FGF21 Improves the Adipocyte Dysfunction Related to Seipin Deficiency. Dollet L, Levrel C, Coskun T, Le Lay S, Le May C, Ayer A, Venara Q, Adams AC, Gimeno RE, Magré J, Cariou* B, Prieur* X. Diabetes 2016;65:3410–3417.

Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode. Dollet L, Magré J, Joubert M, Le May C, Ayer A, Arnaud L, Pecqueur C, Blouin V, Cariou B, Prieur X. Sci Rep 2016;6:35487.  

Funding

This programme has been financed by :

  • Agence Nationale de la Recherche
  • Fondation Francophone pour la Recherche sur le Diabète
  • NEXT
  • Société Francophone du Diabète
  • Société Française de Nutrition
  • Fondation Genavie
  • Fondation pour la Recherche Médicale
  • Fondation de France
  • Région Pays de la Loire
  • SEBIA





1
Mis à jour le 15 January 2024.
https://umr1087.univ-nantes.fr/research/research-teams/adipocyte-dysfunction-and-metabolic-diseases