Synergistic interaction between CCK and leptin to regulate food intake

Leptin administered (either intracerebroventricularly, icv, or intraperiton eally, ip) acts in synergy with CCK to suppress food intake and body weight in lean mice or rats. The potentiating effect induced by the co-injection of ip CCK and leptin to inhibit food consumption in mice is mediated by the CCK-A receptor and capsaicin sensitive afferents. In vitro, studies: in ra ts showed that a subset of gastric vagal afferent fibers responded to lepti n injected directly into the gastric artery only after a prior intra-arteri al CCK injection. Moreover, the tonic activity of gastric-related neurons i n the nucleus tractus solitarius (NTS) increased when leptin was delivered into the gastric chamber of an in vitro stomach-brainstem preparation. CCK co-injected with leptin potentiated Fos expression selectively in the area postrema, NTS and paraventricular nucleus of the hypothalamus (PVN), which points to the PVN as part of the afferent and efferent limbs of the circuit ry involved in the synergistic interaction between leptin and CCK. The damp ening of CCK or leptin inhibitory action on ingestive behavior when either factor is not present or their receptors are non functional supports the no tion that such leptin-CCK interaction may have a physiological relevance. T hese observations provide a mean through which leptin and CCK integrate sho rt- and mid-term meal-related input signals into long-term control of energ y balance. (C) 2000 Elsevier Science B.V. All rights reserved.