“Vitamin D deficiency occurs often in obese people and in patients with Type 2 diabetes, yet no one understands if it contributes to these diseases,” said Stephanie Sisley, MD, the study’s principal investigator and an assistant professor at Baylor College of Medicine, Houston. “Our results suggest that vitamin D may play a role in the onset of both obesity and Type 2 diabetes by its action in the brain.”
“The brain is the master regulator of weight,” Sisley said. A region of the brain called the hypothalamus controls both weight and glucose, and has vitamin D receptors there.
In this study funded by the National Institutes of Health, Sisley and partners at the University of Cincinnati delivered vitamin D directly to the hypothalamus. The investigators administered the active, potent form of vitamin D—called 1,25-dihydroxyvitamin D3—to obese male rats through a cannula (thin tube) surgically inserted using anesthesia into the brain’s third ventricle. This narrow cavity lies within the hypothalamus. Rats recovered their presurgery body weight, and the researchers verified the correct cannula placement.
The animals received nothing to eat for four hours, so they could have a fasting blood sugar measurement. Afterward, 12 rats received vitamin D dissolved in a solution acting as a vehicle for drug delivery. Another 14 rats, matched in body weight to the first group, received only the vehicle, thus serving as controls. One hour later, all rats had a glucose tolerance test, in which they received an injection of dextrose, a sugar, in their abdomen, followed by measurement of their blood sugar levels again.
Compared with the control rats, animals that received vitamin D had improved glucose tolerance, which is how the body responds to sugar. In a separate experiment, these treated rats also had greatly improved insulin sensitivity, the body’s ability to successfully respond to glucose. When this ability decreases—called insulin resistance—it eventually leads to high blood sugar levels. Two of insulin’s main effects are to clear glucose from the bloodstream and decrease glucose production in the liver. In this study, vitamin D in the brain decreased the glucose created by the liver.
In a separate experiment of long-term vitamin D treatment, the researchers gave three rats vitamin D and four rats vehicle alone for four weeks. They observed a large decrease in food intake and weight in rats receiving vitamin D compared with the group that did not get vitamin D. Over 28 days, the treated group ate nearly three times less food and lost 24 percent of their weight despite not changing the way they burned calories, study data showed. The control group did not lose any weight.
“Vitamin D is never going to be the silver bullet for weight loss, but it may work in combination with strategies we know work, like diet and exercise,” Sisley commented.
She said more research is necessary to determine if obesity alters vitamin D transport into the brain or its action in the brain.
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