AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats

Jun 11, 2011Neuroscience letters

Energy sensor activates hunger neurons in the brain to increase eating in rats

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Abstract

24% of hypothalamic arcuate nucleus neurons exhibited increased calcium levels in response to an AMPK activator.

An AMPK activator increased calcium concentration in 24% of monitored ARC neurons.
Phosphorylation of AMPK and acetyl CoA carboxylase occurred in neurons showing calcium responses.
Calcium influx from the extracellular space was responsible for the increase in calcium concentration, as shown by inhibition in calcium-free conditions.
Among responding neurons, 38% were identified as neuropeptide Y (NPY)-immunoreactive, with no proopiomelanocortin (POMC)-immunoreactive neurons present.
Intracerebroventricular administration of the AMPK activator led to increased food intake, which was blocked by an NPY Y1 receptor antagonist.

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AMP-activated protein kinase (AMPK) is an energy sensor that is activated by the increase of intracellular AMP:ATP ratio. AMPK in the hypothalamic arcuate nucleus (ARC) is activated during fasting and the activation of AMPK stimulates food intake. To clarify the pathway underlying AMPK-induced feeding, we monitored the activity of single ARC neurons by measuring cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2 fluorescence imaging. An AMPK activator, AICA-riboside (AICAR), at 200 μM increased [Ca(2+)](i) in 24% of ARC neurons. AMPK and acetyl CoA carboxylase were phosphorylated in the neurons with [Ca(2+)](i) responses to AICAR. AICAR-induced [Ca(2+)](i) increases were inhibited by Ca(2+)-free condition but not by thapsigargin, suggesting that AICAR increases [Ca(2+)](i) through Ca(2+) influx from extracellular space. Among AICAR-responding ARC neurons, 38% were neuropeptide Y (NPY)-immunoreactive neurons while no proopiomelanocortin (POMC)-immunoreactive neuron was observed. Intracerebroventricular administration of AICAR increased food intake, and the AICAR-induced food intake was abolished by the co-administration of NPY Y1 receptor antagonist, 1229U91. These results indicate that the activation of AMPK leads to the activation of ARC NPY neurons through Ca(2+) influx, thereby causing NPY-dependent food intake. These mechanisms could be implicated in the stimulation of food intake by physiological orexigenic substances.

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AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats

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