Hindbrain catecholamine neurons contribute to control of daily food intake during chronic leptin treatment.

Abstract

Chronic leptin treatment sufficient to cause profound reduction of food intake and body weight does not suppress glucoprivic feeding, a control of feeding that requires hindbrain catecholamine neurons. Therefore, we speculated that hindbrain catecholamine neurons may function during leptin treatment to avert brain glucose deficit. If so, elimination of these neurons would potentiate reduction of food intake during chronic leptin treatment. To test this hypothesis, we microinjected the immunotoxin, anti-dopamine beta-hydroxylase saporin (DSAP) or IgG-saporin control (SAP), into the PVH to retrogradely destroy catecholamine neurons with projections to the hypothalamus. This DSAP lesion selectively abolishes the glucoprivic control of feeding, but does not cause anorexia or loss of body weight during ad libitum access to food. Beginning 2 weeks after injections, we administered leptin into the lateral cerebroventricle daily and measured food (standard chow) intake, body weight and plasma metabolic fuels. We found that leptin treatment caused clear changes in plasma NEFA, glycerol and triglyceride levels, but these did not differ between DSAP and SAP rats. However, DSAP lesions significantly reduced food intake during leptin treatment and potentiated leptin-induced weight loss. DSAP-lesioned rats also had lower plasma glucose levels than SAP rats beginning on day 8 of leptin treatment. Results reveal a contribution of hindbrain catecholamine neurons to control of feeding and energy homeostasis during chronic leptin. Catecholamine neurons and/or the glucoprivic control may play a more prominent role in control of daily food intake in the absence of body fat stores.