Reducing hypothalmic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake

Hideo Makimura, Tooru M. Mizuno, Jason W. Mastaitis, Reuven Agami, Charles V. Mobbs

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Background: Several lines of evidence strongly suggest that agouti-related peptide (AGRP) plays a key role in the regulation of metabolic function but ablation of the AGRP gene has no apparent effect on metabolic function. Since specific pharmacological antagonists of AGRP do not presently exist, we assessed if reduction of hypothalamic AGRP mRNA by RNA interference (RNAI) would influence metabolic function, an outcome suggesting that pharmacological antagonists might constitute useful reagents to treat obesity. Results: The RNAI protocol specifically reduced hypothalamic expression of AGRP mRNA by 50% and resulted in reduction of AGRP peptide immunoreactivity. Physiologically, the reduction in AGRP levels was associated with increased metabolic rate and reduced body weight without changes in food intake. Conclusion: AGRP can function to increase body weight and reduce metabolic rate without influencing food intake. The present study demonstrates that RNAI protocols can be used to assess physiological function of neuronal genes in vivo.

Original languageEnglish
Article number18
JournalBMC Neuroscience
Volume3
DOIs
StatePublished - 7 Nov 2002
Externally publishedYes

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