Effects of chronic social defeat stress on peripheral leptin and its hypothalamic actions
1 Department of Biological Production Science, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan
2 Department of Biological Production Science, College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan
3 Kyoto Institute of Nutrition and Pathology Inc., Ujitawara, Kyoto 610-0231, Japan
4 Department of Applied Life Science, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan
5 Department of Bioresorce Science, College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan
BMC Neuroscience 2014, 15:72 doi:10.1186/1471-2202-15-72Published: 6 June 2014
Suppression of body weight and symptom of anorexia are major symptoms of depression. Recently, we reported that chronic social defeat stress (CSDS) induced suppression of body weight gain and anorexic feeding behavior in rats. These abnormalities were the result of disrupted malonyl-coenzyme A (CoA) signaling pathway in the hypothalamus. However, the condition of peripheral leptin and its hypothalamic downstream signal molecules which regulate hypothalamic malonyl-CoA level in the CSDS-exposed rats (CSDS rats) is still unknown.
CSDS rats showed suppressed body weight gain and food intake. The weight of the CSDS rats’ epididymal white adipose tissues was decreased when compared to the control rats. The plasma cholesterol concentration was decreased significantly in the CSDS rats compared to the control rats (P < 0.05). The plasma glucose concentration was slightly decreased in the CSDS rats compared to the control rats (P < 0.1). The expression of leptin mRNA in epididymal white adipose tissues and the plasma leptin concentration were decreased in CSDS rats. Furthermore, the phosphorylation of the hypothalamic downstream signals of leptin, including extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3), was decreased in CSDS rats.
Our results indicated that decreased peripheral leptin expression in CSDS rats could down-regulate the hypothalamic downstream signaling pathways of leptin while suppressed food intake. These data indicate that CSDS induces the down-regulation of hypothalamic AMPK following the elevation of hypothalamic malonyl-CoA levels and is independent of peripheral leptin and glucose.