Objective: To examine the role of AMP-activated protein kinase (AMPK) in the control of glucoprivic feeding by hindbrain catecholamine neurons.
Research design and methods: Micropunched hindbrain samples were collected from control and 2-deoxy-d-glucose (2DG)-injected rats for Western blot analysis of phosphorylated (activated) AMPK (pAMPK). Samples also were collected from 2DG-injected rats pretreated with anti-dopamine-β-hydroxylase conjugated to saporin to lesion hindbrain catecholamine neurons. In a second experiment, rats were given a fourth-ventricle injection of compound C (CC) or 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), an inhibitor and activator of AMPK, to identify a role for AMPK in hindbrain neurons required for elicitation of 2DG-induced feeding.
Results: Systemic 2DG stimulated food intake in controls but not in catecholamine-lesioned rats. In controls, but not catecholamine-lesioned rats, 2DG also increased phosphorylated Thr172 at AMPKα subunits (pAMPKα) in hindbrain micropunches containing catecholaminergic cell groups A1 through the middle region of C1 (A1-C1m). Increased pAMPKα was not observed in the adjacent noncatecholaminergic ventromedial medulla or in the A2-C2 catecholamine cell groups in the dorsal hindbrain. Fourth-ventricle injection of CC attenuated 2DG-induced feeding during the first 2 h of the test, and AICAR alone increased food intake only during the first 60 min of the 4-h test.
Conclusions: Results indicate that AMPK in catecholaminergic A1-C1m neurons is activated by glucoprivation. Therefore, AMPK may contribute to the glucose-sensing mechanism by which these neurons detect and signal a glucose deficit in the service of systemic glucoregulation.