Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight

Authors

Stephanie R. Sisley, Baylor College of Medicine
Deanna M. Arble, Marquette UniversityFollow
Adam P. Chambers, Novo Nordisk, Måløv, Denmark
Ruth Gutierrez-Aguilar, Universidad Nacional Autónoma de México
Yanlin He, Baylor College of Medicine
Yong Xu, Baylor College of Medicine
David Gardner, University of California - San Francisco
David D. Moore, Baylor College of Medicine
Randy J. Seeley, University of Michigan-Ann ArborFollow
Darleen A. Sandoval, University of Michigan - Ann ArborFollow

Document Type

Article

Language

eng

Publication Date

9-2016

Publisher

American Diabetes Association

Source Publication

Diabetes

Source ISSN

0012-1797

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.

Comments

Accepted version. Diabetes, Vol. 65, No. 9 (September 2016): 2732-2741. DOI. © 2016 American Diabetes Association. Used with permission.

Deanna M. Arble was affiliated with the University of Michigan, Ann Arbor at the time of publication.

Recommended Citation

Sisley, Stephanie R.; Arble, Deanna M.; Chambers, Adam P.; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D.; Seeley, Randy J.; and Sandoval, Darleen A., "Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight" (2016). Biological Sciences Faculty Research and Publications. 656.
https://epublications.marquette.edu/bio_fac/656