Participation of Hindbrain AMP-Activated Protein Kinase in Glucoprivic Feeding

Abstract

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.