title: Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.
abstract: We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Morselli
authors.affiliation: Laboratory of Cellular and Molecular Biology, Research Institute of Dental Science and Advanced Center for Chronic Diseases (ACCDiS), Faculty of Dentistry, University of Chile, 8380492 Santiago, Chile.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, 75390-8857, Dallas, Texas, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Navas
authors.affiliation: Cedars-Sinai Diabetes and Obesity Research Institute, Department of Biomedical Research, 90048, Los Angeles, California, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
keywords: 17-β estradiol; Autophagy; Estrogen Receptor α; Lipophagy; Mitophagy; Palmitic Acid; Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α