title: Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight.
abstract: Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei.
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX stephanie.sisley@bcm.edu.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Sisley
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Arble
authors.affiliation: Department of Incretin and Obesity Pharmacology, Novo Nordisk, Måløv, Denmark.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Chambers
authors.affiliation: División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Laboratorio de Enfermedades Metabólicas: Obesidad y Diabetes, Hospital Infantil de México "Federico Gómez," Mexico City, Mexico.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gutierrez-Aguilar
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: He
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA.
authors.forename: David
authors.initials: D
authors.lastname: Gardner
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D059305:Diet, High-Fat / Q000009:adverse effects; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D005947:Glucose