title: Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.
abstract: Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Valdearcos
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Robblee
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Benjamin
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Allison W
authors.initials: AW
authors.lastname: Xu
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: skoliwad@diabetes.ucsf.edu.
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Koliwad
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism; D005227:Fatty Acids / Q000009:adverse effects / Q000378:metabolism*; D005911:Gliosis / Q000209:etiology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D020738:Leptin