Inflammation and metabolism group
Our goal is to understand how immune responses contribute to metabolic health.
Divergent inflammatory responses in skeletal muscle: contributions to physical activity and metabolic diseases.
Obesity and type 2 diabetes are complex multifactorial diseases driven by numerous inherited predispositions and environmental factors. Lifestyle interventions consisting of changes in dietary habits and physical activity are the most efficient strategies to delay the development of metabolic diseases but are often insufficient.
Inadequate activation of the immune system is a core component of metabolic diseases. Our research therefore aims at identifying elements of the immune system that could be leveraged to improve metabolic health.
Meta-analyses of skeletal muscle inflammation and metabolism.
Using bioinformatic approaches to take advantage of the massive amount of data available in public repositories, we generate databases to uncover the molecular response of skeletal muscle to exercise and type 2 diabetes (metamex.eu). The statistical power obtained from such approaches helps identify previously uncharacterised targets and pathways associated with physical activity, metabolic inflammation, obesity and type 2 diabetes.
Identification of molecules regulating skeletal muscle inflammation and metabolism.
Skeletal muscle becomes inflamed under metabolic stress and after exercise and releases cytokines and small soluble factors acting on remote tissues to regulate whole body energy homeostasis. The role of these factors on skeletal muscle inflammation and metabolism and their molecular mechanisms of action are explored using in vitro cultures of primary human skeletal muscle cells and in vivo models of obesity and type 2 diabetes.
Figure. Cross-talks between skeletal muscle and the immune system regulate metabolic inflammation and health. Molecules and cytokines can be released by either immune cells or myocytes during exercise, obesity or type 2 diabetes and reach multiple organs. Understanding the exact roles and mechanisms of action of soluble molecules on inflammatory pathways, glucose and lipid metabolism can open new perspectives for improving metabolic health.
Resources
MetaMEx: Meta-analysis of skeletal muscle response to exercise (metamex.eu)
Selected publications
Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes.
Pillon NJ, Smith JAB, Alm PS, Chibalin AV, Alhusen J, Arner E, Carninci P, Fritz T, Otten J, Olsson T, van Doorslaer de Ten Ryen S, Deldicque L, Caidahl K, Wallberg-Henriksson H, Krook A, Zierath JR
Sci Adv 2022 09;8(36):eabo3192
Metabolic Consequences of Obesity and Type 2 Diabetes: Balancing Genes and Environment for Personalized Care.
Pillon NJ, Loos RJF, Marshall SM, Zierath JR.
Cell. 2021 Mar 18;184(6):1530-1544.
Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism.
Abdelmoez AM, Sardón Puig L, Smith JA, Gabriel BM, Savikj M, Dollet L, Chibalin AV, Krook A, Zierath JR and Pillon NJ.
Am J Physiol Cell Physiol. 2020 Mar 1.
Transcriptomic Profiling of Skeletal Muscle Adaptations to Exercise and Inactivity.
Pillon NJ, Gabriel BM, Dollet L, Smith JA, Botella J, Bishop DJ, Krook A and Zierath JR.
Nat Commun. 2020 Jan 24;11(1):470.
The influence of culture media upon observed cell secretome metabolite profiles: the balance between cell viability and data interpretability.
Daskalakia E, Pillon NJ, Krook A, Wheelock CE, Checa A.
Anal Chim Acta. 2018 Dec 11;1037:338-350.
Skeletal muscle insulin resistance induced by 4-hydroxy-2-hexenal, a by-product of omega-3 fatty acid peroxidation.
Soulage CO, Sardon-Puig L, Soulère L, Zarrouki B, Guichardant M, Lagarde M and Pillon NJ.
Diabetologia. 2018 Mar;61(3):688-699.
Innate Immune Receptors in Skeletal Muscle Metabolism.
Pillon NJ, Krook A.
Exp Cell Res. 2017 Nov 1;360(1):47-54.
Funding - current
- European Foundation for the Study of Diabetes (EFSD) / Novo Nordisk Fonden
- Strategic research program in Diabetes and the Karolinska Institutet
- Diabetes Wellness Sverige
- Forska Utan Djurforsök
Funding – past
- Marie Skłodowska-Curie Actions, European Commission
- O. E. och Edla Johanssons vetenskapliga stiftelse
- Sigurd och Elsa Goljes Foundation
- Lars Hiertas Minne Foundation
- Magnus Bergvalls Foundation