AUTHOR=Campillo Basilio Willem , Galguera David , Cerdan Sebastian , López-Larrubia Pilar , Lizarbe Blanca 

TITLE=Short-term high-fat diet alters the mouse brain magnetic resonance imaging parameters consistently with neuroinflammation on males and metabolic rearrangements on females. A pre-clinical study with an optimized selection of linear mixed-effects models

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.1025108

DOI=10.3389/fnins.2022.1025108

ISSN=1662-453X

ABSTRACT=Obesity and its comorbidities are a current threat to our health care systems, with fundamental sex-dependent biological features shaping its development. High-fat diets (HFDs) are known to trigger an inflammatory response in the brain that prompts the dysregulation of energy balance, leads to insulin and leptin resistance and contributes to obesity development. Neuroinflammation, however, has been principally reported in diet-induced obesity male rodents, with the effects on females remaining unassessed. In this work, we followed the onset of the obese phenotype during control or HFD administrations, in male and female mice. We used physiological markers and magnetic resonance imaging approaches, examining four cerebral regions involved in appetite regulation and energy homeostasis. We investigated the effects of diet, time, region and sex by identifying their significant contributions to sequential linear mixed-effect models, and characterized the corresponding neurochemical profiles by high-resolution magic angle spinning spectroscopy. Results show that male mice developed an obese phenotype paralleled by fast increases in magnetization transfer ratio values, compatible with the development of an early cerebral cytotoxic inflammation. Female animals delayed the obesity progress and showed no MRI-signs of cerebral inflammation, but larger metabolic rearrangements, suggesting the existence of compensatory metabolic adaptations, including decreased glucose metabolism and increased lipid content.