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Effect of 2mercaptoacetate and 2deoxyDglucose administration on the expression of NPY, AGRP, POMC, MCH and hypocretin/orexin in the rat hypothalamus

Sergeyev, Valeriy1; Broberger, Christian1; Gorbatyuk, Oleg1; Hökfelt, Tomas1,2

Neurochemistry

Using in situ hybridization, the mRNA levels encoding neuropeptide Y (NPY), agouti gene-related protein (AGRP), proopiomelanocortin (POMC), melanin-concentrating hormone (MCH) and hypocretin/orexin (HC/ORX) were investigated in the rat arcuate nucleus (Arc) and lateral hypothalamic area (LHA) 2h after a single dose of the glucose antimetabolite 2-deoxy-D-glucose (2-DG; 600 mg/kg) or of the fatty acid oxidation inhibitor mercaptoacetate (MA; 600 μmol/kg). Two hours after 2-DG or MA injection food intake was significantly increased. NPY and AGRP mRNA levels in the Arc were increased by 2-DG but not affected by MA, and MCH mRNA levels in the LHA were increased by both antimetabolites. These results suggest that Arc neurons expressing NPY and AGRP are regulated by changes in glucose, but not fatty acid availability, whereas both factors affect MCH neurons in the LHA.

1Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden

2Corresponding Author: Tomas Hökfelt

Acknowledgements: This study was supported by grants from the Swedish MRC (2887), Marianne and Marcus Wallenberg's Foundation and a Bristol-Myers Squibb Unrestricted Neuroscience Grant. V.S. was supported by a grant from the Swedish Royal Academy of Sciences.

Received 13 October 1999; accepted 25 October 1999

© 2000 Lippincott Williams & Wilkins, Inc.