Leptin Stimulates Catecholamine Synthesis via Tyrosine Hydroxylase Phosphorylation-Dependent and -Independent Pathways in Cultured Bovine Adrenal Medullary Cells

Abstract

Obesity occurs as a consequence of an increased ratio of caloric intake to energy expenditure, and is often associated with cardiovascular and metabolic disorders such as hyperglycemia, hyperlipidemia and hypertension. Although the molecular factors regulating food intake and energy expenditure are not well understood, energy expenditure and body weight are influenced by exercise, physical activity and thermogenesis through the sympathetic nervous system. Leptin, the obese gene product, has been recognized as another mediator of energy expenditure (Zhang et al., 1994). Leptin is secreted from adipose tissues and plays an important role in regulating body weight and food intake through its receptors in the hypothalamus, the center of energy homeostasis (Zhang et al., 1994 ; Tartaglia et al., 1995). Recent studies have shown that leptin acts on peripheral tissues, such as hematopoietic cells, pancreatic islets and the reproductive system, suggesting that leptin also has extrahypothalamic actions. Furthermore, leptin receptors (ObRs) are reported to occur not only in the hypothalamus, but also in various peripheral tissues (Tartaglia et al., 1995; Lee et al., 1996). ObRs are assumed to activate several signal transduction pathways, including the mitogen-activated protein kinase (MAPK) cascade and the Janus protein-tyrosine kinase (JAK)-signal transducers and activators of transcription (STAT) cascade. However, the relation between leptin-induced signal transduction pathway and responses caused by leptin in these tissues remains largely unknown.