Hormonal
Sirt1 activity in Agrp neurons is required for normal ghrelin-induced neuronal firing and food intake.
This finding highlights the critical role of Sirt1 in Agrp neurons for processing hunger signals (ghrelin). It suggests that genetic variations or dysfunction in this specific pathway could impact hunger regulation and body weight, but it does not currently offer a direct intervention for humans.
In accordance with the pharmacological results, the selective knock-out of Sirt1 in hypothalamic Agrp neurons through the use of Cre-Lox technology decreased electric responses of Agrp neurons to ghrelin and decreased food intake, leading to decreased lean mass, fat mass, and body weight.
Why this rating
Genetic knockout models provide strong causal evidence within the mouse model.
Source
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Marcelo O. Dietrich et al. · Journal of Neuroscience · 2010
DOI 10.1523/jneurosci.2234-10.2010
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