[HTML][HTML] Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake
BMC neuroscience, 2002•Springer
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 …
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 …
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.
Springer