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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #305495
Title: CNS Vitamin D improves glucose tolerance, hepatic insulin sensitivity, and reverses diet-induced obesity

Author
item SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC)
item SEELEY, RANDY - University Of Cincinnati
item SANDOVAL, DARLEENE - University Of Cincinnati

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2014
Publication Date: 6/21/2014
Citation: Sisley, S., Seeley, R., Sandoval, D. 2014. CNS Vitamin D improves glucose tolerance, hepatic insulin sensitivity, and reverses diet-induced obesity [abstract]. Endocrine Society Meeting, Oral Session: Vitamin D Metabolism and Action, June 21-24, 2014, Chicago, Illinois. 16486:OR13-1.

Interpretive Summary:

Technical Abstract: Low vitamin D levels have been correlated to both obesity and the development of type 2 diabetes (T2DM) although no causative mechanisms have been established. Vitamin D receptors are present in the hypothalamus, a region important in both weight and glucose regulation. The role of these receptors, though, is unknown. We tested the hypothesis that vitamin D can act in the brain to improve glucose tolerance and weight gain in diet-induced obese animals. 1,25-dihydroxyvitamin D[3], the active form of vitamin D, improved glucose tolerance in DIO rats when given into the third cerebral ventricle (i3vt) 1 hour prior to an intraperitoneal glucose tolerance test. During a hyperinsulinemic euglycemic clamp, i3vt 1,25-dihydroxyvitamin D[3] acutely improved whole body insulin sensitivity, as demonstrated by an 8-fold higher glucose infusion rate in vitamin D treated animals compared to vehicle treated animals (13.19 +/- 0.96 vs. 1.55 +/- 0.62 mg/kg/min; P < 0.0001; n is greater than or equal to 4 per group). I3vt vitamin D[3] suppressed hepatic glucose production to 50% of vehicle treated animals (7.36 +/- 1.98 vs. 16.40 +/- 2.82 mg/kg/min; P = 0.03). This correlated with a 9-fold decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in hepatic gluconeogenesis, in vitamin D treated animals (12.67 +/- 6.86 vs. 118.3 +/- 66.61 ratio of PEPCK:L32; P = 0.009). No changes occurred between groups in glucose clearance (13.59 +/- 0.97 vs, 96 +/- 1.67 mL/kg/min; P = 0.08). Although i3vt 1,25-dihydroxyvitamin D[3] did not change food intake when given acutely, chronic administration dramatically reduced food intake (179.71 +/- 11.27 vs. 484.29 +/- 28.84 g/28 days; P < 0.0001; n is greater than or equal to 3 per group) and body weight (509.87 +/- 9.43 vs. 670.21 +/- 38.05 g; P = 0.014) of DIO animals on a high fat diet without changes in energy expenditure. These results demonstrate the ability of vitamin D to act within the brain to dramatically alter glucose homeostasis and weight maintenance in DIO rats and suggest that vitamin D may play a large role in the onset of both obesity and T2DM.