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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #337864
Title: Hypothalamic vitamin D improves glucose homeostasis and reduces weight

Author
item SISLEY, STEPHANIE - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item ARBLE, DEANNA - UNIVERSITY OF MICHIGAN
item CHAMBERS, ADAM - NOVO NORDISK, INC.
item GUTIERREZ-AGUILAR, RUTH - UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO
item HE, YANLIN - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item XU, YONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item GARDNER, DAVID - UNIVERSITY OF CALIFORNIA
item MOORE, DAVID - BAYLOR COLLEGE OF MEDICINE
item SEELEY, RANDY - UNIVERSITY OF MICHIGAN
item SANDOVAL, DARLEEN - UNIVERSITY OF MICHIGAN

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2016
Publication Date: 9/1/2016
Citation: Sisley, S.R., Arble, D.M., Chambers, A.P., Gutierrez-Aguilar, R., He, Y., Xu, Y., Gardner, D., Moore, D.D., Seeley, R.J., Sandoval, D.A. 2016. Hypothalamic vitamin D improves glucose homeostasis and reduces weight. Diabetes. 65(9):2732-2741.

Interpretive Summary: Low vitamin D levels are associated with both diabetes and obesity but how vitamin D might impact these two diseases is unknown. Understanding how vitamin D affects blood sugar or weight regulation is important in order to use it as a possible treatment. Previous work has shown that the brain is a critical region for both blood sugar and weight control. Additionally, data indicated that the critical receptor for vitamin D action, the vitamin D receptor, was present in the brain. In this paper, we show that the vitamin D receptor is in the key regions of the brain important for blood sugar and weight control. Additionally, we show that vitamin D improves blood sugar control in obese rats and decreases their body weight. These actions of vitamin D are through the vitamin D receptor and are through actions in the brain. This is the first paper describing a role for vitamin D in the brain in the control of blood sugar and weight, and provides a crucial missing link to the association of low vitamin D levels with diabetes and obesity.

Technical 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, 1alpha,25-dihydroxyvitamin D[3] (1,25D[3]) (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 1,25D[3] dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D[3]-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.