Publications de Xiaoxu Li | EPFL Graph Search

Plasmalogen remodeling modulates macrophage response to cytotoxic oxysterols and atherosclerotic plaque vulnerability

Highlights • LPCAT3 and ELOVL5 coordinate PUFA metabolism in macrophages • Dual LPCAT3/ELOVL5 deletion increases membrane cholesterol-enriched domains • This alteration enhances macrophage sensitivity to cytotoxic oxysterols ...

Elsevier BV2025

A lysosomal surveillance response to stress extends healthspan

Johan Auwerx, Yang Li, Wen Gao, Xiaoxu Li, Amélia Lalou, Tanes Imamura de Lima, Qi Wang, Jia Liu

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal ...

Springer Science and Business Media LLC2025

ACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH

Johan Auwerx, Xiaoxu Li, Sandra Rodriguez Lopez, Qi Wang, Jia Liu, Keno Strotjohann

Background & Aims: Recent findings reveal the importance of tryptophan-initiated de novo nicotinamide adenine dinucleotide (NAD+) synthesis in the liver, a process previously considered secondary to biosynthesis from nicotinamide. The enzyme α-amino-β-carb ...

2025

Systems genetics of metabolic health in the BXD mouse genetic reference population

Johan Auwerx, Maroun Bou Sleiman, Wen Gao, Jean-David Horacio Morel, Xiaoxu Li, Alessia De Masi, Amélia Lalou, Jia Liu

Susceptibility to metabolic syndrome (MetS) is dependent on genetics, environment, and gene-by-environment interactions, rendering the study of underlying mechanisms challenging. The majority of experiments in model organisms do not incorporate genetic var ...

2024

High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan

Elena Katsyuba, Johan Auwerx, Laurent Mouchiroud, Maroun Bou Sleiman, Yang Li, Gaby El Alam, Wen Gao, Jean-David Horacio Morel, Xiaoxu Li, Amélia Lalou

Lifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits their translational value for humans. Here, we mapped lifespan determinants in 85 C. e ...

2024

Wars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis

Kristina Schoonjans, Johan Auwerx, Alessia Perino, Hadrien Charles Edouard Demagny, Xiaoxu Li, Antoine Jalil

Several laboratories, including ours, have employed the Slc25a47tm1c(EUCOMM)Hmgu mouse model to investigate the role of SLC25A47, a hepatocyte-specific mitochondrial carrier, in regulating hepatic metabolism and systemic physiology. In this study, we revea ...

2024

Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models

Johan Auwerx, Xiaoxu Li, Alessia De Masi, Tanes Imamura de Lima, Keno Strotjohann

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progress ...

Wiley2024

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass

Johan Auwerx, Yoo Hoon Kim, Maroun Bou Sleiman, Jun Yong Kim, Xiaoxu Li

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocy ...

Nature Portfolio2024

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice

Johan Auwerx, Maroun Bou Sleiman, Jun Yong Kim, Xiaoxu Li

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial ro ...

Nature Portfolio2023

Identifying genetic and dietary modulators of metabolic disorders using systems genetics

Xiaoxu Li

Long-term consumption of lipid-rich foods can contribute to common metabolic diseases and systemic low-grade inflammation. However, dietary responses and the development of non-communicable diseases are shaped by genetic factors and gene-by-environment int ...

EPFL2023

CycloZ reduces inflammation in bleomycin-induced idiopathic pulmonary fibrosis model mice

Johan Auwerx, Xiaoxu Li

European Respiratory Soc Journals Ltd2023

Cyclo(His-Pro): A further step in the management of steatohepatitis

Alexis Rapin, Johan Auwerx, Adrienne Joëlle Laurence Mottis, Xiaoxu Li, Alessia De Masi, Qi Wang

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become the world's most common liver diseases, placing a growing strain on healthcare systems worldwide. Nonetheless, no effective pharmacological treatment has be ...

ELSEVIER2023

CycloZ improves pulmonary fibrosis in bleomycin-induced idiopathic pulmonary fibrosis model mice by modulating the pathogenic transcriptome

Johan Auwerx, Xiaoxu Li

European Respiratory Soc Journals Ltd2023

Inhibition of CERS1 in skeletal muscle exacerbates age-related muscle dysfunction

Olivier Burri, Johan Auwerx, Giacomo Vincenzo Giorgio Von Alvensleben, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Xiaoxu Li, Ludger Jan Elzuë Goeminne, Amélia Lalou, Tanes Imamura de Lima, Barbara Moreira Crisol, Renata Mangione

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate the CERS1 enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis ...

2023

Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging

Johan Auwerx, Hao Li, Mario Romani, Dohyun Park, Pirkka-Pekka Untamo Laurila, Changmyung Oh, Martin Rainer Wohlwend, Jean-David Horacio Morel, Xiaoxu Li, Ludger Jan Elzuë Goeminne, Tanes Imamura de Lima, Sandra Rodriguez Lopez, Barbara Moreira Crisol

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that cer- amide biosynthesis controls the de ...

AMER ASSOC ADVANCEMENT SCIENCE2023

ACMSD INHIBITION REDUCES HEPATIC INFLAMMATION AND FIBROSIS IN A MURINE THERMONEUTRALITY MODEL OF NASH

Johan Auwerx, Richardus Houtkooper, Krisztian Homicsko, Maroun Bou Sleiman, Xiaoxu Li, Sandra Rodriguez Lopez, Jia Liu, Keno Strotjohann

Lippincott Williams & Wilkins2023

Genetic and dietary modulators of the inflammatory response in the gastrointestinal tract of the BXD mouse genetic reference population

Alexis Rapin, Kristina Schoonjans, Johan Auwerx, Alexis Maximilien Bachmann, Maroun Bou Sleiman, Alessia Perino, Jean-David Horacio Morel, Xiaoxu Li

Inflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental, and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment in ...

2023

Lysosomes mediate the mitochondrial UPR via mTORC1-dependent ATF4 phosphorylation

Johan Auwerx, Adrienne Joëlle Laurence Mottis, Yang Li, Wen Gao, Xiaoxu Li, Qi Wang

Lysosomes are central platforms for not only the degradation of macromolecules but also the integration of multiple signaling pathways. However, whether and how lysosomes mediate the mitochondrial stress response (MSR) remain largely unknown. Here, we demo ...

SPRINGERNATURE2023

INHIBITING SARM1 IS MORE EFFICACIOUS THAN NICOTINAMIDE RIBOSIDE SUPPLEMENTATION FOR THE TREATMENT OF A MOUSE MODEL WITH NAFLD/NASH

Johan Auwerx, Richardus Houtkooper, Krisztian Homicsko, Maroun Bou Sleiman, Xiaoxu Li, Sandra Rodriguez Lopez, Jia Liu, Keno Strotjohann

Lippincott Williams & Wilkins2023

The Slc25a47 locus is a novel determinant of hepatic mitochondrial function implicated in liver fibrosis

Kristina Schoonjans, Johan Auwerx, Alessia Perino, Vera Monica Lemos Da Silva, Hao Li, Hadrien Charles Edouard Demagny, Nadia Bresciani, Yu Sun, Xiaoxu Li

Background & Aims: Transporters of the SLC25 mitochondrial carrier superfamily bridge cytoplasmic and mitochondrial metabolism by channeling metabolites across mitochondrial membranes and are pivotal for metabolic homeostasis. Despite their physiological r ...

ELSEVIER2022