J Korean Soc Endocrinol.  2002 Aug;17(4):486-500.

Fos Expression Induced by Combined Injection of Leptin and Cholecystokinin in the Rat Brain

• Kim YU
• You KS
• Kang HS
• Chung CH
• Hwang TS

Abstract

BACKGROUND: Several studies have reported that cholecystokinin (CCK), a short-term meal related satiety signal, and leptin, long-term signal for controlling feeding behaviour and body weight, act synergistically to inhibit food intake. However the mechanism and neuroanatomical basis for this response remain unclear. To clarify the neuronal mechanisms underlying the synergistic interaction between leptin and CCK, we examined the neuron activated by single or combined injection of leptin and CCK in fasted rats using immunohistochemistry for Fos. The expression of Fos can be used to trace neuronal activation pathways.
METHODS
The rats were divided into 4 groups; Tris solution-saline, Tris solution-CCK, leptin-saline, leptin-CCK. Rats were received a single intracerebroventricular injection of either 3mul Tris solution or 3microgram leptin, and a single intraperitoneal injection of either 2mul saline or 2microgram/kg sulfated CCK-8. The changes of the Fos expression were investigated in the paraventricular nucleus (Pa), retrochiasmatic area (RCh), lateral hypothalamic nucleus (LH), central nucleus of amygdala(Ce), supraoptic nucleus (SO), arcuate nucleus (Arc), ventromedial hypothalamic nucleus(VMH),dorsomedial hypothalamic nucleus (DM), ventral premammillary nucleus (PMV), superior lateral subdivision of parabrachial nucleus (LPBS), external lateral subdivision of parabrachial nucleus (LPBE), supragenual nucleus (SGe), area postrema (AP), medial area (SolM) and commissural area (SolC) of nucleus of the solitary tract nuclei.
RESULTS
CCK increased the Fos expression in the Pa, RCh, LH, Ce, SO, Arc, VMH, DM, PMV, LPBS, LPBE and SolM. Leptin increased the Fos expression in the Pa, RCh, LH, SO, Arc, VMH, DM, PMV, LPBS, LPBE, SGe, AP and SolM. Injections of leptin and CCK significantly enhanced the Fos expression in the Pa, RCh, VMH, DM, LPBS, and SolM compared with those induced by leptin or CCK alone.
CONCLUSION
Our results suggest that the Pa, RCh, VMH, DM, LPBS and SolM may be essential sites mediating the synergistic effect of leptin and CCK to regulate food intake.

MeSH Terms

Animals
Arcuate Nucleus
Area Postrema
Body Weight
Brain*
Cholecystokinin*
Eating
Hypothalamic Area, Lateral
Immunohistochemistry
Injections, Intraperitoneal
Leptin*
Meals
Negotiating
Neurons
Paraventricular Hypothalamic Nucleus
Rats*
Sincalide
Solitary Nucleus
Supraoptic Nucleus
Cholecystokinin
Leptin
Sincalide