Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats

  • Authors:
    • Kyoko Goto
    • Akio Inui
    • Yoshiyuki Takimoto
    • Hideki Yuzuriha
    • Akihiro Asakawa
    • Yoshihiro Kawamura
    • Hiroki Tsuji
    • Yukio Takahara
    • Chie Takeyama
    • Goro Katsuura
    • Masato Kasuga
  • View Affiliations

  • Published online on: September 1, 2003     https://doi.org/10.3892/ijmm.12.3.379
  • Pages: 379-383
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Abstract

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments. Oxygen consumption and colonic temperature were measured as indices of energy expenditure, during 3 and 24 h after the ICV injections, respectively. An oral glucose tolerance test was performed 24 h after ICV AgRP (83-132) injection. Binding experiments were performed in HEK-293 cells that over-expressed human MC4-R. AgRP (83-132), but not AgRP (25-51) nor AgRP (54-82), induced a potent and long-lasting increase in the cumulative food intake. Both the carboxyl-terminal and amino-terminal AgRP fragments significantly decreased oxygen consumption and colonic temperature. Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. AgRP causes a potent and long-lasting decrease in energy expenditure; an effect that is exhibited by carboxyl-terminal fragments and amino-terminal fragments that lack antagonist activity at the MC receptors. This suggests that the amino-terminal region of AgRP plays a regulatory role in energy metabolism.

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September 2003
Volume 12 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Goto K, Inui A, Takimoto Y, Yuzuriha H, Asakawa A, Kawamura Y, Tsuji H, Takahara Y, Takeyama C, Katsuura G, Katsuura G, et al: Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats. Int J Mol Med 12: 379-383, 2003.
APA
Goto, K., Inui, A., Takimoto, Y., Yuzuriha, H., Asakawa, A., Kawamura, Y. ... Kasuga, M. (2003). Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats. International Journal of Molecular Medicine, 12, 379-383. https://doi.org/10.3892/ijmm.12.3.379
MLA
Goto, K., Inui, A., Takimoto, Y., Yuzuriha, H., Asakawa, A., Kawamura, Y., Tsuji, H., Takahara, Y., Takeyama, C., Katsuura, G., Kasuga, M."Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats". International Journal of Molecular Medicine 12.3 (2003): 379-383.
Chicago
Goto, K., Inui, A., Takimoto, Y., Yuzuriha, H., Asakawa, A., Kawamura, Y., Tsuji, H., Takahara, Y., Takeyama, C., Katsuura, G., Kasuga, M."Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats". International Journal of Molecular Medicine 12, no. 3 (2003): 379-383. https://doi.org/10.3892/ijmm.12.3.379