Genetic background and sex control the outcome of high-fat diet feeding in mice
Alexis Maximilien Bachmann,
Jean-David Morel,
Gaby El Alam,
Sandra Rodríguez-López,
Tanes Imamura de lima,
Ludger J.E. Goeminne,
Giorgia Benegiamo,
Sylvain Loric,
Marc Conti,
Maroun Bou Sleiman,
Johan Auwerx
Affiliations
Alexis Maximilien Bachmann
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Jean-David Morel
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Gaby El Alam
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Sandra Rodríguez-López
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Tanes Imamura de lima
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Ludger J.E. Goeminne
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Giorgia Benegiamo
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Sylvain Loric
Inserm U938 CRSA, St Antoine University Hospital, Paris, France
Marc Conti
Inserm U938 CRSA, St Antoine University Hospital, Paris, France; Integracell, Longjumeau, France
Maroun Bou Sleiman
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Johan Auwerx
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland; Corresponding author
Summary: The sharp increase in obesity prevalence worldwide is mainly attributable to changes in physical activity and eating behavior but the metabolic and clinical impacts of these obesogenic conditions vary between sexes and genetic backgrounds. This warrants personalized treatments of obesity and its complications, which require a thorough understanding of the diversity of metabolic responses to high-fat diet intake. By analyzing nine genetically diverse mouse strains, we show that much like humans, mice exhibit a huge variety of physiological and biochemical responses to high-fat diet. The strains exhibit various degrees of alterations in their phenotypic makeup. At the transcriptome level, we observe dysregulations of immunity, translation machinery, and mitochondrial genes. At the biochemical level, the enzymatic activity of mitochondrial complexes is affected. The diversity across mouse strains, diets, and sexes parallels that found in humans and supports the use of diverse mouse populations in future mechanistic or preclinical studies on metabolic dysfunctions.
