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Peripheral Administration of Human Corticotropin-Releasing Hormone: A Novel Method to Increase Energy Expenditure and Fat Oxidation in Man¹

Pennington Biomedical Research Center (S.R.S., L.d.J., T.N., R.H., D.Y., S.R., J.R., G.A.B.), Baton Rouge, Louisiana 70808; and Neurocrine Biosciences, Inc. (M.P.), San Diego, California 92121

Address all correspondence and requests for reprints to: Steven R. Smith, M.D., Experimental Endocrinology Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808. E-mail: smithsr{at}pbrc.edu

CRH increases energy expenditure and decreases food intake in experimental animals. We proposed the hypothesis that peripheral administration of CRH might increase energy expenditure in human subjects. Four men and four women (age, 19–39 yr) were randomized to a double blind, cross-over trial to test the effect of human CRH (hCRH), ovine CRH (oCRH), and placebo on resting energy expenditure measured by indirect calorimetry. CRH was administered by primed continuous infusion at progressively increasing doses of 0.5, 1.0, and 2.0 µg/kg·h at 2-h intervals.

hCRH increased resting energy expenditure by 13.9% at the end of the infusion. Respiratory quotient fell from 0.828 to 0.768 during the hCRH infusion compared with a fall from 0.836 to 0.807 during placebo infusion (P < 0.05). Fat oxidation increased by 55% compared with placebo at the highest dose of hCRH. Heart rate increased during hCRH to 10.7 bpm higher than placebo (P < 0.05). oCRH did not increase heart rate. oCRH also had no significant effect on respiratory quotient, and only a small effect on energy expenditure. During hCRH infusion, venous plasma epinephrine, norepinephrine, glycerol, and nonesterified fatty acid levels were not significantly different from those during placebo treatment. Peripheral CRH administration offers a novel strategy to increase energy expenditure.

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