Publications by Maroun Bou Sleiman

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

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

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

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 genetic background shapes the susceptibility to mitochondrial dysfunction and NASH progression

Johan Auwerx, Alexis Maximilien Bachmann, Maroun Bou Sleiman, Giacomo Vincenzo Giorgio Von Alvensleben, Jean-David Horacio Morel, Ludger Jan Elzuë Goeminne, Sandra Rodriguez Lopez

Mice from different genetic backgrounds have widely diverse responses to the same metabolic challenges. Only PWK/PhJ mice show significant mitochondrial dysfunction and progression to fibrotic NASH that resembles human NASH. The PWK/PhJ strain is a novel N ...

ROCKEFELLER UNIV PRESS2023

Mitochondrial and NAD plus metabolism predict recovery from acute kidney injury in a diverse mouse population

Johan Auwerx, Alexis Maximilien Bachmann, Maroun Bou Sleiman, Giacomo Vincenzo Giorgio Von Alvensleben, Dina Hofer, Yang Li, Jean-David Horacio Morel

Acute kidney failure and chronic kidney disease are global health issues steadily rising in incidence and prevalence. Animal models on a single genetic background have so far failed to recapitulate the clinical presentation of human nephropathies. Here, we ...

AMER SOC CLINICAL INVESTIGATION INC2023

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

Sex- and age-dependent genetics of longevity in a heterogeneous mouse population

Johan Auwerx, Maroun Bou Sleiman, Giacomo Vincenzo Giorgio Von Alvensleben, Hao Li, Wen Gao

American Association for the Advancement of Science2022

Article Multi-omics analysis identifies essential regulators of mitochondrial stress response in two wild-type C. elegans strains

Johan Auwerx, Maroun Bou Sleiman, Yang Li, Gaby El Alam, Wen Gao, Amélia Lalou

The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different signaling layers in animals with different geneti ...

CELL PRESS2022

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia

Johan Auwerx, Maroun Bou Sleiman, Peiling Luan, Davide D'Amico, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Sébastien Robert Victor Herzig, Tanes Imamura de Lima, Qi Wang, Barbara Moreira Crisol

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic a ...

2022

Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis

Kristina Schoonjans, Johan Auwerx, Alexis Maximilien Bachmann, Maroun Bou Sleiman, Alessia Perino, Amir Banaei Esfahani, Karim Laurent Gariani, Giacomo Vincenzo Giorgio Von Alvensleben, Hao Li, Qingyao Huang, Laura Alejandra Velazquez Villegas, Yu Sun, Xiaoxu Li, Ludger Jan Elzuë Goeminne

Bile acids (BAs) are complex and incompletely understood enterohepatic-derived hormones that control whole-body metabolism. Here, we profiled postprandial BAs in the liver, feces, and plasma of 360 chowor high-fat-diet-fed BXD male mice and demonstrated th ...

Cell Press2022

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human

Johan Auwerx, Maroun Bou Sleiman, Pooja Jha, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Ludger Jan Elzuë Goeminne, Sandra Rodriguez Lopez

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness. ...

NATURE PORTFOLIO2022

The Genetic Background Shapes Disease Susceptibility And Reveals A Specific Role For Mitochondrial Dysfunction In The Progression From Nafld To Nash

Johan Auwerx, Alexis Maximilien Bachmann, Maroun Bou Sleiman, Giacomo Vincenzo Giorgio Von Alvensleben, Jean-David Horacio Morel, Sandra Rodriguez Lopez, Jia Liu

WILEY2022

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family

Johan Auwerx, Evan Graehl Williams, Maroun Bou Sleiman, Pooja Jha

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a ...

NATURE PORTFOLIO2021

Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome

Maroun Bou Sleiman

Identification of gene expression changes between healthy and diseased individuals can reveal mechanistic insights and biomarkers. Here, the authors propose a bi-directional transcriptome-wide Mendelian Randomization approach to assess causal effects betwe ...

Nature Research2021

The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators

Johan Auwerx, Richardus Houtkooper, Maroun Bou Sleiman, Xu Wang, Pooja Jha

Many genes and pathways have been linked to aging, yet our understanding of underlying molecular mechanisms is still lacking. Here, we measure changes in the transcriptome, histone modifications, and DNA methylome in three metabolic tissues of adult and ag ...

2020

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel

Michael Vincent Frochaux, Bart Deplancke, Dani Osman, Maroun Bou Sleiman, Tommaso Andreani, Riccardo Dainese, Virginie Sandra Braman, Vincent Roland Julien Gardeux, Maria Litovchenko, Brian Dennis Hollis

Background: Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understan ...

2020

Enteric infection induces Lark-mediated intron retention at the 5 ' end of Drosophila genes

Michael Vincent Frochaux, Bart Deplancke, Dani Osman, Maroun Bou Sleiman, Tommaso Andreani

Background RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, we employ a systems approach to study ...

2020